Controlled irrigation for neuromodulation systems and associated methods

ABSTRACT

Neuromodulation catheter systems with controlled irrigation capabilities and methods for using such systems are disclosed herein. One such method includes, for example, positioning an irrigated neuromodulation catheter at a treatment site within a renal blood vessel of a human patient, delivering neuromodulation energy at the treatment site, and delivering irrigation fluid to the treatment site having characteristics coordinated with the delivered energy. The characteristics can be adjusted to maintain an energy delivery element and/or tissue of the blood vessel at a constant temperature as power is increased. The method can further include monitoring at least one parameter of the tissue and/or of the energy delivery element, and adjusting the neuromodulation energy and/or the characteristics of the irrigation fluid if the at least one parameter falls outside of a treatment range of values.

CROSS-REFERENCE TO RELATED APPLICATION(S)

The present application claims the benefit of U.S. Provisional PatentApplication No. 62/621,359, filed Jan. 24, 2018, the disclosure of whichis incorporated herein by reference in its entirety.

TECHNICAL FIELD

The present technology is related to irrigated neuromodulation systemsand associated methods. In particular, various embodiments of thepresent technology are related to neuromodulation catheter systems withcontrolled irrigation capabilities and methods for using such systems.

BACKGROUND

The sympathetic nervous system (SNS) is a primarily involuntary bodilycontrol system typically associated with stress responses. Fibers of theSNS extend through tissue in almost every organ system of the human bodyand can affect characteristics such as pupil diameter, gut motility, andurinary output. Such regulation can have adaptive utility in maintaininghomeostasis or in preparing the body for rapid response to environmentalfactors. Chronic over-activation of the SNS, however, is a commonmaladaptive response that can drive the progression of many diseasestates. Excessive activation of the renal SNS, in particular, has beenidentified experimentally and in humans as a likely contributor to thecomplex pathophysiology of arrhythmias, hypertension, states of volumeoverload (e.g., heart failure), and progressive renal disease.

Sympathetic nerves of the kidneys terminate in the renal blood vessels,the juxtaglomerular apparatus, and the renal tubules, among otherstructures. Stimulation of the renal sympathetic nerves can cause, forexample, increased renin release, increased sodium reabsorption, andreduced renal blood flow. These and other neural-regulated components ofrenal function are considerably stimulated in disease statescharacterized by heightened sympathetic tone. For example, reduced renalblood flow and glomerular filtration rate as a result of renalsympathetic efferent stimulation is likely a cornerstone of the loss ofrenal function in cardio-renal syndrome, (i.e., renal dysfunction as aprogressive complication of chronic heart failure). Pharmacologicstrategies to thwart the consequences of renal sympathetic stimulationinclude centrally-acting sympatholytic drugs, beta blockers (e.g., toreduce renin release), angiotensin-converting enzyme inhibitors andreceptor blockers (e.g., to block the action of angiotensin II andaldosterone activation consequent to renin release), and diuretics(e.g., to counter the renal sympathetic mediated sodium and waterretention). These pharmacologic strategies, however, have significantlimitations including limited efficacy, compliance issues, side effects,and others.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a partially schematic perspective view illustrating a renalneuromodulation system including an irrigated treatment deviceconfigured in accordance with embodiments of the present technology.

FIG. 2A is a partially schematic side view of a neuromodulation catheterwith a distal portion of a guidewire positioned within a blood vessel ofa human patient and configured in accordance with an embodiment of thepresent technology.

FIGS. 2B and 2C are partially schematic side views of theneuromodulation catheter shown in FIG. 2A with an irrigated treatmentassembly in a first state and a second state, respectively, within theblood vessel of the human patient.

FIG. 2D is a front view of the irrigated treatment assembly in thesecond state shown in FIG. 2C looking proximally down a longitudinalaxis of the blood vessel of the human patient.

FIG. 3 is a partially schematic side view of a neuromodulation catheterhaving an irrigated treatment assembly in a deployed state within ablood vessel of a human patient and configured in accordance with anembodiment of the present technology.

FIG. 4 is a partially schematic side view of a neuromodulation catheterhaving an irrigated treatment assembly in a deployed state within ablood vessel of a human patient and configured in accordance with anembodiment of the present technology.

FIG. 5 is a graph depicting an energy delivery algorithm that may beused in conjunction with neuromodulation systems configured inaccordance with embodiments of the present technology.

FIG. 6 is a flow diagram of a process or method for treating a patientusing a neuromodulation system configured in accordance with embodimentsof the present technology.

FIG. 7 illustrates modulating renal nerves and/or evaluating theneuromodulation therapy with the system of FIG. 1 in accordance with anembodiment of the present technology.

FIG. 8 is a conceptual illustration of the sympathetic nervous system(SNS) and how the brain communicates with the body via the SNS.

FIG. 9 is an enlarged anatomic view of nerves innervating a left kidneyto form the renal plexus surrounding the left renal artery.

FIGS. 10 and 11 are anatomic and conceptual views, respectively, of ahuman body depicting neural efferent and afferent communication betweenthe brain and kidneys.

FIGS. 12 and 13 are anatomic views of the arterial vasculature andvenous vasculature, respectively, of a human.

DETAILED DESCRIPTION

The following disclosure describes neuromodulation catheter systems withcontrolled irrigation capabilities and methods for using such systems.More specifically, neuromodulation systems configured in accordance withembodiments of the present technology utilize a neuromodulation catheterhaving an irrigated treatment assembly. The disclosed neuromodulationsystems are configured to deliver coordinated neuromodulation energy andirrigation fluid to the irrigated treatment assembly at a treatment sitewithin a blood vessel (e.g., a renal blood vessel) of a patient. Thedisclosed systems are configured to adjust/modify one or more parametersof energy delivery and irrigation throughout treatment based on, forexample, patient tissue characteristics at the treatment site, treatmentassembly component characteristics, irrigation fluid characteristics,power at which energy is currently being applied, and other relatedparameters.

Using conventional neuromodulation systems and methods, a lesion's depthcan be increased at a target site within a patient by increasing powerat which energy is delivered to the tissue. The temperature of anelectrode (or electrodes) used to deliver such energy, however, alsoincreases as power is increased. In some cases, the increasedtemperature of the electrode can lead to coagulation of blood andcharring of the vessel tissue. This tissue damage can, in turn, lead toother adverse effects, including downstream infarction or otherundesirable tissue damage. For this reason, some conventional systemsincorporate irrigation to provide cooling at the treatment site and toavoid some of the adverse effects experienced with non-irrigatedcatheters. Nevertheless, irrigated ablation systems have been shown tocreate undesirably larger lesions than non-irrigated catheters, andseveral adverse effects associated with tissue damage after use of theseirrigated catheters have been documented, including renal arterystenosis, arterial access site issues, and/or significant eGFR decline.

There are several reasons for the continued presence of adverse effectsassociated with the use of conventional irrigated catheters. Forexample, irrigation fluid in these conventional systems is typicallyapplied in an uncontrolled fashion, with limited control over flow ratesand timing of delivery and limited control over temperature of theinfusate. These practices can skew temperature measurements taken by theneuromodulation system during treatment. In particular, irrigation fluidmay cause these conventional systems to report an electrode temperaturesomewhere between the temperature of the irrigation fluid (e.g., roomtemperature) and a patient's body temperature, which becomesincreasingly inaccurate over the course of treatment (especially aspower is increased). Thus, in many circumstances, any electrodetemperature information conveyed back to the system's generator afteruse of irrigation fluid cannot reliably be used as a measure of ablationprogress. As a result, these conventional irrigated systems inaccuratelytrack the size of the lesions created and the condition of treatedtissue. Although this issue not as much of a concern when ablatingcertain anatomical structures (e.g., heart tissue), this lack of controlis especially problematic when ablating near electrically vulnerable,thin-walled, or other arterial structures. For example, renal anatomy istypically more complicated in the local heterogeneity of anatomicalstructures than heart tissue. Thus, greater control and care whenperforming renal denervation is required than can be offered byconventional irrigated systems.

In contrast with conventional systems and techniques, neuromodulationsystems and methods in accordance with embodiments of the presenttechnology are configured to deliver coordinated neuromodulation energyand irrigation fluid to a treatment site. In some embodiments, thesesystems and methods are configured to actively monitor characteristics(e.g., temperature, impedance, etc.) of the tissue and/or of theneuromodulation element(s) at the treatment site. The systems andmethods can use this diagnostic information to monitor treatmentprogress and/or to adjust (i) characteristics (e.g., type, power level,duration, frequency, etc.) of neuromodulation energy applied to thetreatment site in relation to a control algorithm of the neuromodulationprocedure and/or (ii) characteristics (e.g., volume, temperature, type,duration, rate, etc.) of the irrigation fluid delivered to the treatmentsite. Accordingly, systems configured in accordance with the presenttechnology are expected to achieve greater control of lesioncharacteristics during the neuromodulation procedure and to improve thelikelihood that the neuromodulation procedure will be successful,especially in blood vessels with impaired and/or low blood flow. Forexample, systems and methods in accordance with embodiments of thepresent technology are expected to achieve greater lesion depth withoutthe adverse effects noticed in patients after use of conventionalsystems and methods.

Specific details of several embodiments of the present technology aredescribed herein with reference to FIGS. 1A-13. Although many of theembodiments are described with respect to devices, systems, and methodsfor intravascular renal neuromodulation, other applications and otherembodiments in addition to those described herein are within the scopeof the present technology. For example, at least some embodiments of thepresent technology may be useful for extravascular neuromodulation,intravascular non-renal neuromodulation, and/or use in therapies otherthan neuromodulation. It should be noted that other embodiments inaddition to those disclosed herein are within the scope of the presenttechnology. Further, embodiments of the present technology can havedifferent configurations, components, and/or procedures than those shownor described herein. Moreover, a person of ordinary skill in the artwill understand that embodiments of the present technology can haveconfigurations, components, and/or procedures in addition to those shownor described herein and that these and other embodiments can be withoutseveral of the configurations, components, and/or procedures shown ordescribed herein without deviating from the present technology.

As used herein, the terms “distal” and “proximal” define a position ordirection with respect to a clinician or a clinician's control device(e.g., a handle of a neuromodulation catheter). The terms, “distal” and“distally” refer to a position distant from or in a direction away froma clinician or a clinician's control device along the length of device.The terms “proximal” and “proximally” refer to a position near or in adirection toward a clinician or a clinician's control device along thelength of device. The headings provided herein are for convenience onlyand should not be construed as limiting the subject matter disclosed.

A. Selected Embodiments of Neuromodulation Catheters and Systems

FIG. 1 is a partially-schematic diagram illustrating a neuromodulationsystem 100 configured in accordance with an embodiment of the presenttechnology. The system 100 can include a treatment device 110 (e.g., anirrigated catheter) operably coupled to a console 102 via a connector101 (e.g., a cable). The system 100 further includes an irrigation pump104 integrated with the console 102 to facilitate simultaneous and/orcoordinated delivery of neuromodulation energy and irrigation fluidduring therapy. As shown in FIG. 1, the treatment device 110 can includean elongated shaft 112 having a proximal portion 114, a handle assembly111 at a proximal region of the proximal portion 114, and a distalportion 116 extending distally relative to the proximal portion 114. Theelongated shaft 112 can be configured to locate the distal portion 116intravascularly (e.g., within a renal artery) or within another suitablebody lumen (e.g., within a ureter) at a treatment location. Thetreatment device 110 can further include a treatment assembly 120carried by or affixed to the distal portion 116 of the elongated shaft112. The treatment assembly 120 can include one or more neuromodulationelements 126 (shown schematically in FIG. 1) configured to deliver atherapeutic energy or compound to a nerve located at least proximate toa wall of a body lumen. In some embodiments, the handle 111 can includean actuator 113 to convert the treatment assembly 120 between a deliverystate and a deployed state via a guide wire (not shown) and remoteactuation of the actuator 113.

The console 102 can be configured to control, monitor, supply, orotherwise support operation of the treatment device 110. For example,the console 102 can include an energy generator operably connected tothe neuromodulation element(s) 126 and configured to generate a selectedform and magnitude of therapeutic, neuromodulation energy (e.g.,radiofrequency energy (“RF”), pulsed energy, microwave energy, opticalenergy, direct heat energy, or another suitable type of energy) fordelivery to the treatment site via the neuromodulation element(s) 126 toalter, damage, or disrupt nerves.

In some embodiments, the console 102 can be configured to store and/ortransmit (via the connector 101 and/or the elongated shaft 112)irrigation fluid (e.g., saline, distilled water, etc.) to the treatmentassembly 120. As noted previously, for example, the console 102 includesthe irrigation pump 104 to transfer irrigation fluid from the console102 to the treatment assembly 120 of the treatment device 110. In otherembodiments, the system 100 can include a neuromodulation console (notshown) and a separate irrigation console (not shown) containing theirrigation pump 104 and/or a storage container (not shown) to storeirrigation fluid. In these embodiments, the neuromodulation console canbe communicatively coupled to the irrigation console. As described ingreater detail below, the system 100 can facilitate simultaneous and/orcoordinated delivery of neuromodulation energy and irrigation fluid tothe treatment assembly 120. To reduce the likelihood of tissue damageand/or associated adverse effects, the irrigation fluid can be used tocool (i) tissue at the treatment site and/or (ii) components of thetreatment assembly 120.

The console 102 can be electrically coupled to the treatment device 110via the connector 101 (e.g., a cable). One or more supply wires (notshown) can pass along the elongated shaft 112 or through a lumen in theelongated shaft 112 to the neuromodulation element(s) 126 to transmitthe neuromodulation energy to the neuromodulation element(s) 126. Inaddition, one or more fluid supply lumens (not shown) can pass along theelongated shaft 112 or through a lumen in the elongated shaft 112 to thetreatment assembly 120. The fluid supply lumen(s) can transmitirrigation fluid to one or more irrigation outlets (not shown) in thetreatment assembly 120.

The console 102 can also be configured to deliver neuromodulation energyand/or irrigation fluid to the treatment assembly 120 in accordance withan automated control algorithm 150 and/or under the control of aclinician. The control algorithm 150 may be executed on a processor (notshown) of the system 100. One or more sensors (e.g., pressure,temperature, impedance, flow, chemical, ultrasound, electromagnetic,etc.) of the treatment assembly 120 and/or of the treatment device 110can generate diagnostic information/measurements regarding patienttissue at the treatment site and/or regarding components of thetreatment assembly 120. The diagnostic information can be used asfeedback for the control algorithm 150 and can allow the system 100 toadjust the control algorithm 150 (e.g., based on a comparison of thediagnostic information to predetermined parameter profile ranges). Inparticular, the system 100 can adjust characteristics (e.g., type, powerlevel, duration, frequency, etc.) of neuromodulation energy delivered tothe neuromodulation element(s) 126 and/or characteristics (e.g., volume,temperature, type, rate, duration, etc.) of irrigation fluid deliveredto the treatment assembly 120. The diagnostic information can alsoprovide feedback to the clinician, such as via an indicator 105 (e.g., adisplay, a user interface, one or more LEDs, etc.) associated with theconsole 102 and/or the system 100. For example, the console 102 mayinclude a user interface that can receive user input and/or provide thediagnostic information to the user. The feedback from the diagnosticinformation can allow a clinician to determine the effectiveness of theapplied energy during the treatment and/or shortly thereafter (e.g.,while the patient is still catheterized). Likewise, while the patient isstill catheterized, a clinician may decide to repeat, pause, and/orterminate treatment based on feedback from the diagnostic information(e.g., to avoid tissue damage). Accordingly, this feedback may be usefulin helping the clinician increase the likelihood of success of thecurrent or subsequent treatments and/or avoid adverse effects of thetreatment(s). Further details regarding a suitable control algorithm 150are described below with reference to FIG. 5.

The system 100 can include a controller 106 having, for example, memory(not shown), storage devices (e.g., disk drives), one or more outputdevices (e.g., a display), one or more input devices (e.g., a keyboard,a touchscreen, etc.), and/or processing circuitry (not shown). Thecontroller 106 can be configured to execute, adjust, and/or modify thecontrol algorithm 150. For example, the output devices may be configuredto communicate with the treatment device 110 (e.g., via the connector101) to control power to the neuromodulation element(s) 126 and/or tocontrol supply of irrigation fluid to the treatment assembly 120. Insome embodiments the output devices can further be configured to obtainsignals from the neuromodulation element(s) 126 and/or any associatedsensors. Display devices may be configured to provide indications ofpower levels or sensor data, such as audio, visual, or otherindications, and/or the display devices may be configured to communicatethe information to another device.

In some embodiments, the controller 106 can be part of the console 102,as shown in FIG. 1. Additionally or alternatively, the controller 106can be personal computer(s), server computer(s), handheld or laptopdevice(s), multiprocessor system(s), microprocessor-based system(s),programmable consumer electronic(s), digital camera(s), network PC(s),minicomputer(s), mainframe computer(s), tablets, and/or any suitablecomputing environment. The memory and storage devices arecomputer-readable storage media that may be encoded with non-transitory,computer-executable instructions (e.g., the control algorithm 150, thefeedback algorithm(s), etc.). In addition, the instructions, datastructures, and message structures may be stored or transmitted via adata transmission medium, such as a signal on a communications link andmay be encrypted. Various communication links may be used, such as theInternet, a local area network, a wide area network, a point-to-pointdial-up connection, a cell phone network, Bluetooth, RFID, and othersuitable communication channels. The system 100 may be described in thegeneral context of computer-executable instructions, such as programmodules, executed by one or more computers or other devices. Generally,program modules include routines, programs, objects, components, datastructures, and so on that perform particular tasks or implementparticular abstract data types. Typically, the functionality of theprogram modules may be combined or distributed as desired in variousembodiments.

The neuromodulation element(s) 126 of the treatment assembly 120 can beconfigured to modulate one or more nerves (e.g., renal nerves) withintissue at or at least proximate to a wall of a vessel or lumen. Asdescribed in greater detail below, the neuromodulation element(s) 126can include one or more energy delivery elements (e.g., electrodes;FIGS. 2A-4) and/or one or more sensors (e.g., to monitor the energydelivery elements and/or tissue at the treatment site). For example, insome embodiments, the neuromodulation element(s) 126 can include asingle energy delivery element located at a distal portion 116 of thetreatment device 110. In other embodiments, the neuromodulationelement(s) 126 can include two or more energy delivery elements. Theenergy delivery elements can be separate band electrodes spaced apartfrom each other along a portion of the length of the shaft 112. Theelectrodes can be adhesively bonded to a support structure at differentpositions along the length of the shaft 112. In some embodiments, theenergy delivery elements can be formed from a suitable electricallyconductive material (e.g., a metal, such as gold, platinum, alloys ofplatinum and iridium, etc.). The number, arrangement, shape (e.g.,spiral and/or coil electrodes) and/or composition of the energy deliveryelements may vary. The individual energy delivery elements of theneuromodulation element(s) 126 can be electrically connected to thehandle assembly 111 and/or the console 102 by a conductor or bifilarwire extending through a lumen of the shaft 112.

In embodiments having multiple energy delivery elements, the energydelivery elements may deliver power independently (e.g., may be used ina monopolar fashion), either simultaneously, selectively, orsequentially, and/or may deliver power between any desired combinationof the elements (e.g., may be used in a bipolar fashion). Furthermore,the clinician optionally may be permitted to choose which energydelivery element(s) are used for power delivery in order to form highlycustomized lesion(s) within the vessel (e.g., the renal artery) or otherbody lumens (e.g., the ureter), as desired. In some embodiments, thesystem 100 may be configured to provide delivery of a monopolar electricfield via the neuromodulation element(s) 126. In such embodiments, aneutral or dispersive electrode 109 may be electrically connected to theconsole 102 and attached to the exterior of the patient.

FIGS. 2A-2C are partially schematic side views of a neuromodulationcatheter 210 (e.g., the treatment device 110 shown in FIG. 1) configuredin accordance with an embodiment of the present technology. Theneuromodulation catheter 210 is shown in different arrangements in FIGS.2A-2C while positioned at a treatment site within a blood vessel V(e.g., a renal artery) of a human patient. The neuromodulation catheter210 includes a guidewire 215 (only visible in FIG. 2A) and an irrigatedtreatment assembly 220 that can be advanced over the guidewire 215 tothe treatment site within the blood vessel V. The irrigated treatmentassembly 220 is configured to perform neuromodulation therapy at thetreatment site to, for example, ablate nerves proximate the wall of theblood vessel V. As discussed in greater detail below, the irrigatedtreatment assembly 220 can be configured to monitor tissue of the bloodvessel V at the treatment site and components (e.g., neuromodulationelement(s) 226) of the irrigated treatment assembly 220. For example,one or more sensors (not shown) of the irrigated treatment assembly 220are configured to gather diagnostic information and measurementsrelating to the temperature of the tissue and/or the neuromodulationelement(s) 226 during neuromodulation treatment of the tissue. Thediagnostic information can be used as feedback to adjust characteristicsof neuromodulation energy delivery and/or characteristics of irrigationfluid delivery to the irrigated treatment assembly 220.

The guidewire 215 includes an elongated member 218 having a distalportion 218 a configured to be positioned at the treatment site withinthe blood vessel V and a proximal portion (not visible) that extendsoutside of the patient to a handle (e.g., the handle 111 shown inFIG. 1) or other feature(s) that allow an operator to manipulate thedistal portion 218 a to the desired position/orientation (e.g., usingthe actuator 113 shown in FIG. 1). The elongated member 218 can be sizedto be slidably positioned within a lumen of the neuromodulation catheter210. In other embodiments, the elongated member 218 comprises othersuitable components (e.g., sensor(s)) and/or configurations.Additionally, the elongated member 218 can have a uniform stiffnessalong its length, or can have a stiffness that varies along its length.

As best shown in FIG. 2B, the elongated shaft 112 of the neuromodulationcatheter 210 is configured to be slidably delivered over the guidewire215. The elongated shaft 112 has a distal portion 116 configured to beintravascularly positioned at the treatment site within the blood vesselV and a proximal portion 114 extending outside of the patient to ahandle (e.g., the handle 111 shown in FIG. 1) or other features thatallow an operator to manipulate the distal portion 116 of the elongatedshaft 112 (e.g., using the actuator 113 shown in FIG. 1). As shown inFIGS. 2B and 2C, for example, the irrigated treatment assembly 220 ofthe neuromodulation catheter 210 is transformable between a first stateor arrangement in which the distal portion 116 of the elongated shaft112 is at least generally straight low-profile delivery arrangement(FIG. 2B), and a second (e.g., deployed, expanded, etc.) state orarrangement in which the distal portion 116 is transformed or otherwiseexpanded to a spiral/helical shape (FIG. 2C). In some embodiments, thetreatment assembly 220 can have a shape memory corresponding to thesecond state, and the guidewire 215 (FIG. 2A) can retain the treatmentassembly 220 in the first state until the guidewire 215 is at leastpartially removed (e.g., withdrawn). The dimensions (e.g., outerdiameter and length) of the distal portion 116 of the elongated shaft112 (e.g., the portion that takes on the spiral/helical shape in thesecond state illustrated in FIG. 2C) can be selected to accommodate thevessels or other body lumens in which the distal portion 116 is designedto be delivered. For example, when in the second state, the axial lengthof the distal portion 116 of the elongated shaft 112 may be selected tobe no longer than a patient's renal artery (e.g., typically less than 7cm), and have a diameter that accommodates the inner diameter of atypical renal artery (e.g., about 2-10 mm). In other embodiments, thedistal portion 116 of the elongated shaft 112 can have other dimensionsdepending on the body lumen within which it is configured to bedeployed. In other embodiments, the distal portion 116 of the elongatedshaft 112 can have other suitable shapes (e.g., semi-circular, curved,straight, etc.), sizes, and/or configurations. Other suitable devicesand technologies are described in, for example, U.S. Pat. Nos.8,777,942; 9,084,610; 9,060,755; 8,998,894; PCT Application No.PCT/US2011/057754, filed Oct. 25, 2011; and U.S. Pat. No. 8,888,773. Allof the foregoing applications are incorporated herein by reference intheir entireties. One non-limiting example of a device and systemincludes the Symplicity Spyral™ multielectrode RF ablation catheter.

Referring to FIGS. 2B and 2C together, the irrigated treatment assembly220 includes four neuromodulation elements 226 spaced along the distalportion 116 of the elongated shaft 112. In other embodiments, however,the irrigated treatment assembly 220 may include one, two, three, ormore than four neuromodulation element(s) 226 and/or may includemultiple support members configured to carry one or more neuromodulationelements 226. Each neuromodulation element 226 in the illustratedembodiment includes an electrode 224 (identified individually as firstthrough fourth electrodes 224 a-224 d, respectively). Neuromodulationelements 226 in other embodiments can include a greater and/or lessernumber of electrodes 224. In some embodiments, the neuromodulationelements 226 can include one or more sensors configured to monitortissue at the treatment site and/or components (e.g., the electrodes 224a-224 d) of the treatment assembly 220.

The electrodes 224 a-224 d are configured to deliver neuromodulationenergy (e.g., RF energy) to tissue at or at least proximate to thevessel wall V at the treatment site to modulate one or more nerves(e.g., renal nerves) within the tissue when the irrigated treatmentassembly 220 is in the second state illustrated in FIG. 2C. In thisstate, the distal portion 116 of the elongated shaft 112 may be designedto apply a desired outward radial force to the blood vessel V to placeone or more of the electrodes 224 a-224 d in contact with the vesselwall. In these and other embodiments, the irrigated treatment assembly220 can include electrodes, transducers, or other elements to deliverother suitable neuromodulation modalities, such as pulsed electricalenergy, microwave energy, optical energy, ultrasound energy (e.g.,intravascularly delivered ultrasound and/or high-intensity focusedultrasound (HIFU)), direct heat energy, radiation (e.g., infrared,visible, and/or gamma radiation), and/or other suitable types of energyto alter, damage, or disrupt nerves.

As explained above, the treatment assembly 220 and/or one or more of theneuromodulation elements 226 can include one or more sensors (not shown)configured to monitor characteristics of tissue, such as temperature, atthe treatment site and/or of components (e.g., the electrodes 224 a-224d and/or the neuromodulation element(s) 226) of the treatment assembly220. In some embodiments, the one or more sensors can be directlyincorporated into the neuromodulation element(s) 226 (e.g., into and/orproximal to the electrodes 224 a-224 d) of the irrigated treatmentassembly. In these and other embodiments, the one or more sensors can belocated at various locations along the elongated shaft 112 of theneuromodulation catheter 210 and/or apart from the neuromodulationelement(s) 226 of the irrigated treatment assembly 220. The one or moresensors can be configured to measure and/or generate diagnosticinformation regarding tissue of the blood vessel V and/or components ofthe neuromodulation element(s) 226 of the irrigated treatment assembly220. For example, the one or more sensors can continuously and/orperiodically measure temperature, pressure, time, impedance, power, flowvelocity, volumetric flow rate, blood pressure, heart rate, parametersof return energy, or other parameters of the neuromodulation catheter210 and/or patient tissue at the treatment site. Through thesemeasurements, the one or more sensors generate diagnostic informationthat can be reported back to one or more controller(s) 106 of the system100, as described in greater detail below.

As best shown in FIGS. 2B and 2C, the irrigated treatment assembly 220can include one or more irrigation outlets 222 at the distal portion 216of the elongated shaft 112. The irrigation outlets 222 can be connectedto one or more fluid supply lumens (not shown) that extend along theelongated shaft 112 (or through a lumen in the elongated shaft 112) toan irrigation pump (e.g., the irrigation pump shown in FIG. 1) and/or astorage container (not shown). As explained above, irrigation fluid(e.g., saline, distilled water, etc.) can be transmitted via the fluidsupply lumens to the treatment assembly 220 and can be released at thetreatment site via the irrigation outlets 222. In this manner, theneuromodulation catheter 210 can cool components (e.g., theneuromodulation element(s) 226) of the irrigated treatment assembly 220and/or tissue at the treatment site (e.g., during neuromodulationtreatment).

The irrigation outlets 222 can be arranged at various points around thecircumference of the elongated shaft 112 (as best shown in FIG. 2B) suchthat the irrigation outlets 222 are positioned in a desired orientationwhen the treatment assembly 220 is in the second state (shown in FIG.2C). For example, the irrigation outlets 222 can be arranged such thatthey direct irrigation fluid distally along or generally along alongitudinal axis L of the blood vessel V (as shown in FIGS. 2C and 2D).In other embodiments, the irrigation outlets 222 can be oriented to facein one or more different directions (e.g., to face in a directionopposite the direction illustrated in FIGS. 2C and 2D, to face thevessel wall, and/or to face toward the center of the blood vessel V)when the treatment assembly 220 is in the second state. In operation,the system 100 can release irrigation fluid proximal to the wall of theblood vessel V and/or proximal to the electrodes 224 a-224 d via theirrigation outlets 222. Irrigation fluid released from an irrigationoutlet 222 thus can provide cooling to (i) tissue of the vessel walland/or (ii) components of the treatment assembly 220 near the irrigationoutlet 222. In addition, irrigation fluid released from the irrigationoutlets 222 can be carried along the vessel wall by blood flowingthrough the blood vessel V. Therefore, irrigation fluid released from anirrigation outlet 222 can also provide cooling to (i) tissue of thevessel wall, (ii) components of the treatment assembly 220, and/or (iii)components of the neuromodulation catheter 210 located downstream fromthe irrigation outlet 222.

Although the irrigation outlets 222 illustrated in FIGS. 2A-2D arepositioned proximal to the electrodes 224 a-224 d of the treatmentassembly 220, one or more of the irrigation outlets 222 can bepositioned at other locations and/or in different arrangements in otherembodiments of the present technology. For example, FIGS. 3 and 4 arepartially schematic side views of neuromodulation catheters 310 and 410,respectively, configured in accordance with other embodiments of thepresent technology. As shown in FIG. 3, the neuromodulation catheter 310includes an irrigated treatment assembly 320 having irrigation outlets322 (e.g., the irrigation outlets 222 shown in FIGS. 2A-2D) at locationsalong the elongated shaft 112 that are more proximal to the proximalportion 114 of the elongated shaft 112 than the locations of theirrigation outlets 222 illustrated in FIGS. 2A-2D. The irrigationoutlets 322 are positioned about the circumference of the elongatedshaft 112 and are configured to release irrigation fluid radiallyoutward from the elongated shaft 112. Additionally or alternatively, theirrigation outlets 322 can be shaped and/or fluid supply lumens coupledto the irrigation outlet(s) 322 can be oriented within the elongatedshaft 112 such that irrigation fluid is output from the irrigationoutlets 322 in a desired direction away from the irrigated outlets 322.

In other embodiments and as shown in FIG. 4, the neuromodulationcatheter 410 can include an irrigated treatment assembly 420 having anirrigation ring/donut element 430 with one or more irrigation outlets422. The irrigation ring element 430 is configured to expand radiallyoutward from the elongated shaft 112 such that the irrigation ring 430surrounds the elongated shaft 112 and is proximal to or engages an innervessel wall. As shown, one or more fluid supply lumens 434 can extend(e.g., from the elongated shaft 112) into the irrigation ring element430. The irrigation outlets 422 and/or the fluid supply lumens 434 canbe (i) oriented to direct irrigation fluid down a longitudinal axis L ofthe blood vessel V, (ii) oriented to face the vessel wall and/or anotherdirection, (iii) configured to direct irrigation toward the vessel wall,and/or (iv) shaped and/or oriented within the irrigation ring element430 such that irrigation fluid is output from the irrigation ringelement 430 in a desired direction away from the irrigation outlets 422.

As discussed above, neuromodulation catheters 210, 310, and 410configured in accordance with embodiments of the present technology canbe communicatively coupled to one or more controller(s) 106 of theconsole 102 (FIG. 1) via a wired or wireless communication link. In someembodiments, one or more of the controller(s) 106 may be separate fromthe console, such as in embodiments where the irrigation pump 104 shownin FIG. 1 is separate from the console 102. The controller(s) 106 can beconfigured to initiate, terminate, and/or adjust operation of one ormore components (e.g., the electrodes 224 a-224 d) of the treatmentassemblies 220, 320, and 420 directly and/or via the console 102. Forexample, the controller(s) 106 may be configured to continuously orintermittently monitor tissue of the blood vessel wall and/or componentsof the treatment assemblies 220, 320, and 420 using diagnosticinformation from the one or more sensors (not shown) of the treatmentassemblies 220, 320, and 420. More specifically, the controller 106 canuse the diagnostic information to adjust (i) characteristics of theneuromodulation energy and/or (ii) characteristics of irrigation fluiddelivered to the treatment assemblies 220, 320, and 420 (e.g., inaccordance with a control algorithm). Thus, the controller(s) 106 can beconfigured to control, monitor, supply, adjust, and/or otherwise supportoperation of the neuromodulation catheters 210, 310, and 410 based atleast in part on the diagnostic information generated by the one or moresensors of the treatment assemblies 220, 320, and 420.

B. Control of Applied Energy and Irrigation Characteristics

As discussed above, neuromodulation systems (e.g., the system 100 shownin FIG. 1) configured in accordance with embodiments of the presenttechnology can be configured to deliver coordinated neuromodulationenergy (e.g., RF energy) and irrigation fluid to a treatment assembly ofa treatment device in accordance with an automated control algorithm 150and/or under the control of a clinician. FIG. 5 shows one embodiment ofan automated control algorithm 150 that may be implemented by acontroller 106 (e.g., the controller 106 shown in FIGS. 1-4). As shownin FIG. 5, when a clinician initiates treatment, the control algorithm150 can include instructions that cause a console (e.g., the console 102shown in FIG. 1) to gradually adjust the power of energy applied to atreatment site to a first power level P₁ (e.g., 5 watts) over a firsttime period t₁ (e.g., 15 seconds). The power can increase generallylinearly during the first time period. As a result, the console canincrease its power output at a generally constant rate of P₁/t₁.Alternatively, the power may increase non-linearly (e.g., exponential orparabolic) with a variable rate of increase.

Additionally or alternatively, the control algorithm 150 can includeinstructions that coordinate delivery of irrigation fluid to thetreatment site before, during, and/or after neuromodulation energy isapplied to the treatment site, adjusted, and/or modified. For example,the control algorithm 150 can include instructions that direct thesystem (e.g., a console and/or an irrigation pump) to deliver irrigationfluid with characteristics corresponding to the increase in power to thefirst power level P₁. In some embodiments, the instructions can directthe system to deliver a specific type (e.g., saline, distilled water,etc.) and/or volume of irrigation fluid to the treatment site. In theseand other embodiments, the instructions can direct the system to (i)deliver irrigation fluid at a specified temperature (e.g., roomtemperature, body temperature, or another temperature above or belowroom temperature), (ii) deliver irrigation fluid at a specified flowrate, and/or (ii) deliver irrigation fluid for a specified duration. Inthese and still other embodiments, instructions can direct the system toadjust (e.g., increase, decrease, change, and/or terminate) any of theseirrigation fluid characteristics as the power is adjusted (e.g.,increased, decreased, and/or held constant). In still other embodiments,the control algorithm 150 can include instructions to refrain fromdelivering irrigation fluid until a specified power level is reached, aspecified electrode temperature is reached, and/or for a specifiedperiod of time.

Once P₁ and t₁ are achieved, the control algorithm 150 may hold at P₁until a new time t₂ for a predetermined period of time t₂-t₁ (e.g., 3seconds). The control algorithm 150 may similarly hold the irrigationfluid characteristics constant until t₂ and/or may adjust the irrigationfluid characteristics (e.g., based on monitored parameters of the tissueat the treatment site and/or of components of the treatment device, asdescribed in greater detail below). At t₂, power is increased by apredetermined increment (e.g., 1 watt) to P₂ over a predetermined periodof time, t₃-t₂ (e.g., 1 second). The control algorithm 150 can includeinstructions directing the system to adjust irrigation fluidcharacteristics in accordance with this power increase. The power rampin predetermined increments of about 1 watt over predetermined periodsof time may continue until a maximum power P_(MAX) is achieved or someother condition is satisfied (e.g., a maximum irrigation flowrate/volume and/or a minimum irrigation fluid temperature is reached).Optionally, the power may be maintained at the maximum power P_(MAX) fora desired period of time or up to the desired total treatment time(e.g., up to about 120 seconds). In these and other embodiments, thecontroller can continually change the irrigation fluid characteristicsbased on, for example, (i) monitored parameters of the tissue at thetreatment site and/or of the components of the treatment device and/or(ii) the progress of the neuromodulation procedure.

Furthermore and before, during, and/or after the neuromodulationprocedure, the controller can monitor (e.g., using one or more sensorsof the treatment assembly) one or more parameters corresponding totissue at the treatment site, to the patient, to the irrigation fluid,and/or to components (e.g., neuromodulation elements) of a treatmentdevice. For example, the controller can continuously or periodicallymonitor temperature, time, impedance, power, flow velocity, volumetricflow rate, blood pressure, heart rate, parameters of return energy,and/or other parameters. The controller can use diagnosticinformation/measurements of the parameters as feedback regarding theprogress of the neuromodulation procedure, the state (e.g., temperature)of treatment device components, and/or of the condition of the tissue atthe treatment site. In some embodiments, the controller (i) can checkthe monitored parameters against predetermined parameter profiles todetermine whether the parameters individually or in combination fallwithin the ranges set by the predetermined parameter profiles, and (ii)can accordingly coordinate and/or adjust characteristics of theneuromodulation energy and/or of irrigation fluid delivered to thetreatment site. For example, the controller can check whether themonitored parameters fall within ranges set by the predeterminedparameter profiles given certain neuromodulation energy characteristicsand/or irrigation fluid characteristics. If the monitored parametersfall within the ranges, then treatment may continue in accordance withthe control algorithm 150. If the monitored parameters fall outside theranges, however, the controller can adjust the control algorithm 150accordingly.

For example, if temperature measurements relating to the tissue at thetreatment site and/or to components (e.g., the neuromodulation elements)of the treatment device are too high for a currently applied powerlevel, the controller can adjust and/or modify the control algorithm 150(e.g., until the parameters are within the parameter profile range(s)).In some embodiments, the controller can decrease, pause, and/orterminate the applied power; can lengthen or shorten t₁, t₂, t₃, etc. ofthe control algorithm 150; and/or can modify the duty cycle, frequency,or other parameters of the control algorithm 150. Additionally oralternatively, the controller can change characteristics of theirrigation fluid delivered to the treatment site. For example, thecontroller can increase and/or decrease the flow rate of, the volume of,and/or the temperature of the irrigation fluid delivered to thetreatment site. In these and other embodiments, the controller canchange the type of irrigation fluid released at the treatment siteand/or the duration for which irrigation fluid is applied to thetreatment site. It will be appreciated by those skilled in the art thatthe controller can adjust (e.g., increase, decrease, alter, adjust,and/or otherwise change) or hold constant the control algorithm 150 inresponse to other events noted by the control algorithm 150. Forexample, the controller can appropriately adjust the control algorithm150 in response to (i) one or more parameters outside of (e.g., aboveand/or below) predetermined parameter profile range(s); and/or (ii) asudden, unexpected, and/or undesired change in measuredparameters/characteristics of the tissue and/or of the components of thetreatment device (e.g., even when the parameters/characteristics fallwithin the parameter profile range(s)). The system may also be equippedwith various audible and visual alarms to allow the controller to alertthe operator of certain conditions.

In some embodiments, the system can include one or more safetythresholds that prevent the controller from adjusting characteristics ofthe energy and/or of the irrigation fluid above and/or below thethresholds. For example, while the neuromodulation energy is applied ator above a specified power level and/or for longer than a specifiedduration, the system can prevent the controller from (i) decreasing theflow rate below a specified threshold and/or (ii) increasing thetemperature of the irrigation fluid above a specified threshold. Inother embodiments, to prevent the system (e.g., one or more sensors onneuromodulation elements of the treatment device) from reporting aninaccurate (e.g., temperature) measurement regarding components of thetreatment device and/or the tissue at the treatment site, the system canprevent the controller from (i) increasing the flow rate of theirrigation fluid above a specified threshold and/or (ii) decreasing thetemperature of the irrigation fluid below a specified threshold. Instill other embodiments, the system can prevent the controller fromincreasing the power level of the neuromodulation energy above aspecified threshold (e.g., when the maximum flow rate and/or volume ofirrigation fluid supplied to the treatment site is reached and/or whenthe minimum temperature of irrigation fluid is reached).

In this manner, the controller can deliver coordinated neuromodulationenergy and irrigation fluid to the treatment site. As a result, thecontroller can hold the temperature of the neuromodulation elementsconstant and/or within a desired range through controlled and/orcontinued use of irrigation fluid having desired characteristics. Thispermits the neuromodulation system to achieve greater lesion depths byincreasing the power of the neuromodulation energy applied to the bloodvessel without coagulation of blood or charring of the vessel tissueassociated with elevated electrodes temperatures during therapy. Themaximum power that can safely be delivered to the patient during therapyis therefore increased. In particular, neuromodulation systemsconfigured in accordance with the present technology permit power to besafely increased until a maximum power level of the energy generator isachieved, until a maximum irrigation flow rate/volume is achieved, untila minimum irrigation fluid temperature is achieved, and/or until thesystem otherwise prevents the controller from increasing the powerfurther (e.g., in accordance with preset safety thresholds). In someembodiments, the maximum irrigation flow rate and/or volume can bedetermined by (i) irrigation pump capacity; (ii) a patient's blooddilution limit (ensuring adequate blood supply to an end-organ); (iii)safety factors determined from pre-clinical models, general humananatomical knowledge, specific patient anatomy, and/or ablationlocation; and/or (v) achievement of specific lesion depth. In addition,because irrigation fluid is applied in a controlled manner (e.g., onlywhen needed, with desired characteristics, and/or at flow ratestypically less than conventional irrigated systems) throughout theneuromodulation procedure, diagnostic information reported to thecontroller regarding the progress of the neuromodulation procedure, thecondition of the tissue at the treatment site, and/or the condition ofcomponents of the treatment device remain meaningful and accurate. As aresult, the neuromodulation system of the present technology is betterable to avoid tissue damage and adverse effect of neuromodulationtreatment typically noted after use of conventional neuromodulationsystems.

FIG. 6 is a flow diagram illustrating a routine 670 directed to a methodof treating a patient configured in accordance with embodiments of thepresent technology. The routine 670 can be performed by, for example,various components of the neuromodulation system (e.g., a console, acontroller, a control algorithm, an irrigation pump, and/or a treatmentdevice) and/or a clinician operating the neuromodulation system. Theroutine 670 can begin at block 671 by positioning a treatment assemblyof a treatment device intravascularly (e.g., within a renal artery) orwithin another suitable body lumen (e.g., within a ureter) within apatient. The routine 670 can further includes deploying the treatmentassembly (e.g., by withdrawing a guidewire) at a treatment site withinthe patient.

At block 672, the routine 670 can include delivering neuromodulationenergy via neuromodulation elements of the treatment assembly to tissueat the treatment site (e.g., in accordance with a control algorithm ofthe neuromodulation system). At block 673, the routine 670 canadditionally or alternatively include delivering irrigation fluid havingdesired characteristics via irrigation outlets in the treatmentassembly. Delivery of the irrigation fluid can be controlled, forexample, in accordance with the control algorithm. For example, theroutine 670 can (i) deliver neuromodulation energy at a first powerlevel after and/or over a first period of time and/or (ii) deliver afirst type of irrigation fluid with desired characteristics (e.g., at afirst volume, temperature, and/or flow rate) corresponding to the rampin power. In some embodiments, the routine 670 can deliver irrigationfluid having specified characteristics to hold the temperature ofneuromodulation elements on the treatment assembly within a desiredtemperature range. In these and other embodiments, the routine 670 canrefrain from delivering irrigation fluid to the treatment site until theneuromodulation energy reaches a specified power level and/or until theneuromodulation elements and/or tissue at the treatment site reach aspecified temperature.

In some embodiments, the routine 670 can continue to increase the powerof the neuromodulation energy and/or to modify the characteristics ofthe irrigation fluid delivered to the treatment site in accordance withthe control algorithm. For example, the routine 670 can increase thepower of the neuromodulation energy to a second power level (e.g., aftera second period of time) and apply the neuromodulation energy to tissueat the treatment site at the second power level (block 672).Additionally, the routine 670 can adjust and/or modify thecharacteristics of the irrigation fluid delivered to the treatment sitein accordance with this power increase. For example, the routine 670 canincrease the volume and/or flow rate of irrigation fluid delivered tothe treatment site as the power of the neuromodulation energy isincreased (block 673). In these and other embodiments, the routine 670can decrease the temperature at which the irrigation fluid is suppliedto the treatment site and/or can alter the type of irrigation fluidsupplied to the treatment site (block 673). In other embodiments, theroutine 670 (i) can keep the irrigation fluid characteristics constant,(ii) stop delivery of irrigation fluid to the treatment site, and/or(iii) wait to adjust and/or modify the characteristics of the irrigationfluid supplied to the treatment site until the second power level isreached and/or until the neuromodulation elements reach a specifiedtemperature (block 673).

In some embodiments, the routine 670 can continue to deliverneuromodulation energy and/or irrigation fluid in accordance with thecontrol algorithm until a maximum power value and/or other safetythresholds of the neuromodulation system is/are reached (blocks 672 and673). At this point, the routine 670 can prevent an increase in power ifa maximum volume and/or flow rate of irrigation fluid is reached.Additionally or alternatively, the routine 670 can prevent an increasein power if a minimum temperature of irrigation fluid is reached and/ora maximum temperature of the neuromodulation elements is reached.

At any point before, during, and/or after positioning and/or deployingthe treatment assembly, the routine 670 can monitor (e.g., continuouslyand/or simultaneously) one or more parameters relating to the patientand/or to components (e.g., neuromodulation elements and/or electrodes)of the neuromodulation system (block 674). For example, the routine 670can use one or more sensors located on or near neuromodulation elementsof the treatment device to measure the temperature, impedance, duration,power, flow velocity, volumetric flow rate, blood pressure, heart rate,parameters of return energy, and/or other parameters of the tissue atthe treatment site, of the patient, of the irrigation fluid, and/or ofthe neuromodulation elements of the treatment device. The routine 670can use this diagnostic information as feedback regarding the progressof a neuromodulation procedure (e.g., the size and/or depth of a lesionformed during treatment), the condition of the tissue at the treatmentsite, and/or the condition of components of the neuromodulation system.

In some embodiments, the routine 670 can determine whether to adjustand/or modify one or more characteristics of the neuromodulation energyapplied to the treatment site and/or of the irrigation fluid supplied tothe treatment site, respectively, based at least in part on thediagnostic information. For example, the routine 670 can compare thediagnostic information to predetermined parameter profile ranges todetermine if one or more parameters are outside of those range(s). Ifspecific parameters and/or a predetermined number of parameters fallwithin the parameter profile ranges, the routine 670 can continue toapply neuromodulation energy and/or irrigation fluid in accordance withthe control algorithm (blocks 672 and/or 673).

On the other hand, if one or more of the parameters fall outside (e.g.,above and/or below) the predetermined parameter profile ranges, theroutine 670 can decide to adjust and/or modify one or morecharacteristics of the neuromodulation energy (block 675) and/or of theirrigation fluid (block 676) applied to the treatment site. For example,if the routine 670 determines the temperature of the tissue at thetreatment site and/or of the neuromodulation elements is above thepredetermined temperature profile range (e.g., given the current energycharacteristics, the current stage in the neuromodulation procedure, thecurrent irrigation fluid characteristics, and/or safety threshold(s)),the routine 670 can alter and/or modify the control algorithm to alterand/or modify the power level of the neuromodulation energy (block 675).In some embodiments, the routine 670 can decrease the power at whichneuromodulation energy is applied. In other embodiments, the routine 670can hold the power level constant and/or can increase the power level ata slower rate. Additionally or alternatively, the routine 670 can alterand/or modify the control algorithm to alter and/or modify theirrigation fluid characteristics (e.g., block 676). For example, theroutine 670 can (i) increase the volume and/or flow rate of theirrigation fluid applied at the treatment site, (ii) decrease thetemperature at which the irrigation fluid is applied at the treatmentsite, and/or (iii) change the type of irrigation fluid applied to thetreatment site. In some embodiments, the routine 670 can (i) increasethe power of the neuromodulation energy and/or the temperature of theirrigation fluid applied to the treatment site and/or (ii) decrease thevolume and/or flow rate of the irrigation fluid only after the one ormore parameters move back within the predetermined parameter profilerange(s).

Although the steps of the routine 670 are discussed and illustrated in aparticular order, the method illustrated by the routine 670 is not solimited. In other embodiments, the method can be performed in adifferent order. For example, one or more sensors of the neuromodulationsystem can monitor parameters of the neuromodulation system and/or ofthe patient before energy and/or irrigation fluid is delivered to thetreatment site. In other embodiments, irrigation fluid can be applied tothe treatment site before neuromodulation energy is applied to thetreatment site and/or adjusted. In these and other embodiments, theneuromodulation system may require that an increase in power applied tothe treatment site be proceeded by and/or be applied simultaneously with(i) an increase in the volume and/or flow rate of irrigation fluidapplied to the treatment site and/or (ii) a decrease in the temperatureof irrigation fluid. Moreover, blocks 671-676 are illustrated for thesake of completeness. A person skilled in the art will readily recognizethat the illustrated method can be altered and still remain within theseand other embodiments of the present technology. For example, one ormore steps of the method illustrated in FIG. 6 can be omitted and/orrepeated in some embodiments.

C. Selected Examples of Neuromodulation Devices and Related Systems

FIG. 7 (with additional reference to FIG. 1) illustrates modulatingrenal nerves in accordance with an embodiment of the system 100 (FIG.1). The neuromodulation device 110 provides access to the renal plexusRP through an intravascular path P, such as a percutaneous access sitein the femoral (illustrated), brachial, radial, or axillary artery to atargeted treatment site within a respective renal artery RA. Bymanipulating the proximal portion 114 of the elongated shaft 112 fromoutside the intravascular path P, a clinician may advance the elongatedshaft 112 through the sometimes tortuous intravascular path P andremotely manipulate the distal portion 116 (FIG. 1) of the elongatedshaft 112. In the embodiment illustrated in FIG. 7, the neuromodulationassembly 120 is delivered intravascularly to the treatment site using aguidewire 715 in an OTW technique. At the treatment site, the guidewire715 can be at least partially withdrawn or removed, and theneuromodulation assembly 120 can transform or otherwise be moved to adeployed arrangement for recording neural activity and/or deliveringenergy at the treatment site. In other embodiments, the neuromodulationassembly 120 may be delivered to the treatment site within a guidesheath (not shown) with or without using the guidewire 715. When theneuromodulation assembly 120 is at the treatment site, the guide sheathmay be at least partially withdrawn or retracted and the neuromodulationassembly 120 can be transformed into the deployed arrangement. In otherembodiments, the elongated shaft 112 may be steerable itself such thatthe neuromodulation assembly 120 may be delivered to the treatment sitewithout the aid of the guidewire 715 and/or the guide sheath.

Image guidance, e.g., computed tomography (CT), fluoroscopy,intravascular ultrasound (IVUS), optical coherence tomography (OCT),intracardiac echocardiography (ICE), or another suitable guidancemodality, or combinations thereof, may be used to aid the clinician'spositioning and manipulation of the neuromodulation assembly 120. Forexample, a fluoroscopy system (e.g., including a flat-panel detector,x-ray, or c-arm) can be rotated to accurately visualize and identify thetarget treatment site. In other embodiments, the treatment site can bedetermined using IVUS, OCT, and/or other suitable image mappingmodalities that can correlate the target treatment site with anidentifiable anatomical structure (e.g., a spinal feature) and/or aradiopaque ruler (e.g., positioned under or on the patient) beforedelivering the neuromodulation assembly 120. Further, in someembodiments, image guidance components (e.g., IVUS, OCT) may beintegrated with the neuromodulation device 110 and/or run in parallelwith the neuromodulation device 110 to provide image guidance duringpositioning of neuromodulation assembly 120. For example, image guidancecomponents (e.g., IVUS or OCT) can be coupled to neuromodulationassembly 120 to provide three-dimensional images of the vasculatureproximate the treatment site to facilitate positioning or deploying themulti-electrode assembly within the target renal vascular structure.

Energy from the neuromodulation elements 126 may then be applied totarget tissue to induce one or more desired neuromodulating effects onlocalized regions of the renal artery RA and adjacent regions of therenal plexus RP, which lay intimately within, adjacent to, or in closeproximity to the adventitia of the renal artery RA. The purposefulapplication of the energy may achieve neuromodulation along all or atleast a portion of the renal plexus RP. The neuromodulating effects aregenerally a function of, at least in part, power, time, contact betweenthe energy delivery elements and the vessel wall, and blood flow throughthe vessel. The neuromodulating effects may include denervation, thermalablation, and/or non-ablative thermal alteration or damage (e.g., viasustained heating and/or resistive heating). Desired thermal heatingeffects may include raising the temperature of target neural fibersabove a desired threshold to achieve non-ablative thermal alteration, orabove a higher temperature to achieve ablative thermal alteration. Forexample, the target temperature may be above body temperature (e.g.,approximately 37° C.) but less than about 45° C. for non-ablativethermal alteration, or the target temperature may be about 45° C. orhigher for the ablative thermal alteration. Desired non-thermalneuromodulation effects may include altering the electrical signalstransmitted in a nerve.

Hypothermic effects may also provide neuromodulation. For example, acryotherapeutic applicator may be used to cool tissue at a treatmentsite to provide therapeutically-effective direct cell injury (e.g.,necrosis), vascular injury (e.g., starving the cell from nutrients bydamaging supplying blood vessels), and sublethal hypothermia withsubsequent apoptosis. Exposure to cryotherapeutic cooling can causeacute cell death (e.g., immediately after exposure) and/or delayed celldeath (e.g., during tissue thawing and subsequent hyperperfusion).Embodiments of the present technology can include cooling a structure ator near an inner surface of a renal artery wall such that proximate(e.g., adjacent) tissue is effectively cooled to a depth wheresympathetic renal nerves reside. For example, the cooling structure iscooled to the extent that it causes therapeutically effective, cryogenicrenal-nerve modulation. Sufficiently cooling at least a portion of asympathetic renal nerve is expected to slow or potentially blockconduction of neural signals to produce a prolonged or permanentreduction in renal sympathetic activity.

D. Renal Neuromodulation

Renal neuromodulation is the partial or complete incapacitation or othereffective disruption of nerves of the kidneys (e.g., nerves terminatingin the kidneys or in structures closely associated with the kidneys). Inparticular, renal neuromodulation can include inhibiting, reducing,and/or blocking neural communication along neural fibers (e.g., efferentand/or afferent neural fibers) of the kidneys. Such incapacitation canbe long-term (e.g., permanent or for periods of months, years, ordecades) or short-term (e.g., for periods of minutes, hours, days, orweeks). Renal neuromodulation is expected to contribute to the systemicreduction of sympathetic tone or drive and/or to benefit at least somespecific organs and/or other bodily structures innervated by sympatheticnerves. Accordingly, renal neuromodulation is expected to be useful intreating clinical conditions associated with systemic sympathetic overactivity or hyperactivity, particularly conditions associated withcentral sympathetic overstimulation. For example, renal neuromodulationis expected to efficaciously treat hypertension, heart failure, acutemyocardial infarction, metabolic syndrome, insulin resistance, diabetes,left ventricular hypertrophy, chronic and end stage renal disease,inappropriate fluid retention in heart failure, cardio-renal syndrome,polycystic kidney disease, polycystic ovary syndrome, osteoporosis,erectile dysfunction, and sudden death, among other conditions.

Renal neuromodulation can be electrically-induced, thermally-induced,chemically-induced, or induced in another suitable manner or combinationof manners at one or more suitable treatment sites during a treatmentprocedure. The treatment site can be within or otherwise proximate to arenal lumen (e.g., a renal artery, a ureter, a renal pelvis, a majorrenal calyx, a minor renal calyx, or another suitable structure), andthe treated tissue can include tissue at least proximate to a wall ofthe renal lumen. For example, with regard to a renal artery, a treatmentprocedure can include modulating nerves in the renal plexus, which layintimately within or adjacent to the adventitia of the renal artery.

Renal neuromodulation can include a cryotherapeutic treatment modalityalone or in combination with another treatment modality. Cryotherapeutictreatment can include cooling tissue at a treatment site in a mannerthat modulates neural function. For example, sufficiently cooling atleast a portion of a sympathetic renal nerve can slow or potentiallyblock conduction of neural signals to produce a prolonged or permanentreduction in renal sympathetic activity. This effect can occur as aresult of cryotherapeutic tissue damage, which can include, for example,direct cell injury (e.g., necrosis), vascular or luminal injury (e.g.,starving cells from nutrients by damaging supplying blood vessels),and/or sublethal hypothermia with subsequent apoptosis. Exposure tocryotherapeutic cooling can cause acute cell death (e.g., immediatelyafter exposure) and/or delayed cell death (e.g., during tissue thawingand subsequent hyperperfusion). Neuromodulation using a cryotherapeutictreatment in accordance with embodiments of the present technology caninclude cooling a structure proximate an inner surface of a body lumenwall such that tissue is effectively cooled to a depth where sympatheticrenal nerves reside. For example, in some embodiments, a coolingassembly of a cryotherapeutic device can be cooled to the extent that itcauses therapeutically-effective, cryogenic renal neuromodulation. Inother embodiments, a cryotherapeutic treatment modality can includecooling that is not configured to cause neuromodulation. For example,the cooling can be at or above cryogenic temperatures and can be used tocontrol neuromodulation via another treatment modality (e.g., to protecttissue from neuromodulating energy).

Renal neuromodulation can include an electrode-based or transducer-basedtreatment modality alone or in combination with another treatmentmodality. Electrode-based or transducer-based treatment can includedelivering electricity and/or another form of energy to tissue at atreatment location to stimulate and/or heat the tissue in a manner thatmodulates neural function. For example, sufficiently stimulating and/orheating at least a portion of a sympathetic renal nerve can slow orpotentially block conduction of neural signals to produce a prolonged orpermanent reduction in renal sympathetic activity. A variety of suitabletypes of energy can be used to stimulate and/or heat tissue at atreatment location. For example, neuromodulation in accordance withembodiments of the present technology can include delivering RF energy,pulsed energy, microwave energy, optical energy, focused ultrasoundenergy (e.g., high-intensity focused ultrasound energy), or anothersuitable type of energy alone or in combination. An electrode ortransducer used to deliver this energy can be used alone or with otherelectrodes or transducers in a multi-electrode or multi-transducerarray. Furthermore, the energy can be applied from within the body(e.g., within the vasculature or other body lumens in a catheter-basedapproach) and/or from outside the body (e.g., via an applicatorpositioned outside the body). Furthermore, energy can be used to reducedamage to non-targeted tissue when targeted tissue adjacent to thenon-targeted tissue is subjected to neuromodulating cooling.

Neuromodulation using focused ultrasound energy (e.g., high-intensityfocused ultrasound energy) can be beneficial relative to neuromodulationusing other treatment modalities. Focused ultrasound is an example of atransducer-based treatment modality that can be delivered from outsidethe body. Focused ultrasound treatment can be performed in closeassociation with imaging (e.g., magnetic resonance, computed tomography,fluoroscopy, ultrasound (e.g., intravascular), optical coherencetomography, or another suitable imaging modality). For example, imagingcan be used to identify an anatomical position of a treatment location(e.g., as a set of coordinates relative to a reference point). Thecoordinates can then entered into a focused ultrasound device configuredto change the power, angle, phase, or other suitable parameters togenerate an ultrasound focal zone at the location corresponding to thecoordinates. The focal zone can be small enough to localizetherapeutically-effective heating at the treatment location whilepartially or fully avoiding potentially harmful disruption of nearbystructures. To generate the focal zone, the ultrasound device can beconfigured to pass ultrasound energy through a lens, and/or theultrasound energy can be generated by a curved transducer or by multipletransducers in a phased array (curved or straight).

Heating effects of electrode-based or transducer-based treatment caninclude ablation and/or non-ablative alteration or damage (e.g., viasustained heating and/or resistive heating). For example, a treatmentprocedure can include raising the temperature of target neural fibers toa target temperature above a first threshold to achieve non-ablativealteration, or above a second, higher threshold to achieve ablation. Thetarget temperature can be higher than about body temperature (e.g.,about 37° C.) but less than about 45° C. for non-ablative alteration,and the target temperature can be higher than about 45° C. for ablation.Heating tissue to a temperature between about body temperature and about45° C. can induce non-ablative alteration, for example, via moderateheating of target neural fibers or of vascular or luminal structuresthat perfuse the target neural fibers. In cases where vascularstructures are affected, the target neural fibers can be deniedperfusion resulting in necrosis of the neural tissue. Heating tissue toa target temperature higher than about 45° C. (e.g., higher than about60° C.) can induce ablation, for example, via substantial heating oftarget neural fibers or of vascular or luminal structures that perfusethe target fibers. In some patients, it can be desirable to heat tissueto temperatures that are sufficient to ablate the target neural fibersor the vascular or luminal structures, but that are less than about 90°C. (e.g., less than about 85° C., less than about 80° C., or less thanabout 75° C.).

Renal neuromodulation can include a chemical-based treatment modalityalone or in combination with another treatment modality. Neuromodulationusing chemical-based treatment can include delivering one or morechemicals (e.g., drugs or other agents) to tissue at a treatmentlocation in a manner that modulates neural function. The chemical, forexample, can be selected to affect the treatment location generally orto selectively affect some structures at the treatment location overother structures. The chemical, for example, can be guanethidine,ethanol, phenol, a neurotoxin, or another suitable agent selected toalter, damage, or disrupt nerves. A variety of suitable techniques canbe used to deliver chemicals to tissue at a treatment location. Forexample, chemicals can be delivered via one or more needles originatingoutside the body or within the vasculature or other body lumens. In anintravascular example, a catheter can be used to intravascularlyposition a therapeutic element including a plurality of needles (e.g.,micro-needles) that can be retracted or otherwise blocked prior todeployment. In other embodiments, a chemical can be introduced intotissue at a treatment location via simple diffusion through a body lumenwall, electrophoresis, or another suitable mechanism. Similar techniquescan be used to introduce chemicals that are not configured to causeneuromodulation, but rather to facilitate neuromodulation via anothertreatment modality.

E. Related Anatomy and Physiology

As noted previously, the sympathetic nervous system (SNS) is a branch ofthe autonomic nervous system along with the enteric nervous system andparasympathetic nervous system. It is always active at a basal level(called sympathetic tone) and becomes more active during times ofstress. Like other parts of the nervous system, the sympathetic nervoussystem operates through a series of interconnected neurons. Sympatheticneurons are frequently considered part of the peripheral nervous system(PNS), although many lie within the central nervous system (CNS).Sympathetic neurons of the spinal cord (which is part of the CNS)communicate with peripheral sympathetic neurons via a series ofsympathetic ganglia. Within the ganglia, spinal cord sympathetic neuronsjoin peripheral sympathetic neurons through synapses. Spinal cordsympathetic neurons are therefore called presynaptic (or preganglionic)neurons, while peripheral sympathetic neurons are called postsynaptic(or postganglionic) neurons.

At synapses within the sympathetic ganglia, preganglionic sympatheticneurons release acetylcholine, a chemical messenger that binds andactivates nicotinic acetylcholine receptors on postganglionic neurons.In response to this stimulus, postganglionic neurons principally releasenoradrenaline (norepinephrine). Prolonged activation may elicit therelease of adrenaline from the adrenal medulla.

Once released, norepinephrine and epinephrine bind adrenergic receptorson peripheral tissues. Binding to adrenergic receptors causes a neuronaland hormonal response. The physiologic manifestations include pupildilation, increased heart rate, occasional vomiting, and increased bloodpressure. Increased sweating is also seen due to binding of cholinergicreceptors of the sweat glands.

The sympathetic nervous system is responsible for up- anddown-regulating many homeostatic mechanisms in living organisms. Fibersfrom the SNS innervate tissues in almost every organ system, providingat least some regulatory function to physiological features as diverseas pupil diameter, gut motility, and urinary output. This response isalso known as sympatho-adrenal response of the body, as thepreganglionic sympathetic fibers that end in the adrenal medulla (butalso all other sympathetic fibers) secrete acetylcholine, whichactivates the secretion of adrenaline (epinephrine) and to a lesserextent noradrenaline (norepinephrine). Therefore, this response thatacts primarily on the cardiovascular system is mediated directly viaimpulses transmitted through the sympathetic nervous system andindirectly via catecholamines secreted from the adrenal medulla.

Science typically looks at the SNS as an automatic regulation system,that is, one that operates without the intervention of consciousthought. Some evolutionary theorists suggest that the sympatheticnervous system operated in early organisms to maintain survival as thesympathetic nervous system is responsible for priming the body foraction. One example of this priming is in the moments before waking, inwhich sympathetic outflow spontaneously increases in preparation foraction.

1. The Sympathetic Chain

As shown in FIG. 8, the SNS provides a network of nerves that allows thebrain to communicate with the body. Sympathetic nerves originate insidethe vertebral column, toward the middle of the spinal cord in theintermediolateral cell column (or lateral horn), beginning at the firstthoracic segment of the spinal cord and are thought to extend to thesecond or third lumbar segments. Because its cells begin in the thoracicand lumbar regions of the spinal cord, the SNS is said to have athoracolumbar outflow. Axons of these nerves leave the spinal cordthrough the anterior rootlet/root. They pass near the spinal (sensory)ganglion, where they enter the anterior rami of the spinal nerves.However, unlike somatic innervation, they quickly separate out throughwhite rami connectors which connect to either the paravertebral (whichlie near the vertebral column) or prevertebral (which lie near theaortic bifurcation) ganglia extending alongside the spinal column.

In order to reach the target organs and glands, the axons should travellong distances in the body, and, to accomplish this, many axons relaytheir message to a second cell through synaptic transmission. The endsof the axons link across a space, the synapse, to the dendrites of thesecond cell. The first cell (the presynaptic cell) sends aneurotransmitter across the synaptic cleft where it activates the secondcell (the postsynaptic cell). The message is then carried to the finaldestination.

In the SNS and other components of the peripheral nervous system, thesesynapses are made at sites called ganglia, discussed above. The cellthat sends its fiber is called a preganglionic cell, while the cellwhose fiber leaves the ganglion is called a postganglionic cell. Asmentioned previously, the preganglionic cells of the SNS are locatedbetween the first thoracic (TI) segment and third lumbar (L3) segmentsof the spinal cord. Postganglionic cells have their cell bodies in theganglia and send their axons to target organs or glands.

The ganglia include not just the sympathetic trunks but also thecervical ganglia (superior, middle and inferior), which sendssympathetic nerve fibers to the head and thorax organs, and the celiacand mesenteric ganglia (which send sympathetic fibers to the gut).

a. Innervation of the Kidneys

As FIG. 9 shows, the kidney is innervated by the renal plexus (RP),which is intimately associated with the renal artery. The renal plexus(RP) is an autonomic plexus that surrounds the renal artery and isembedded within the adventitia of the renal artery. The renal plexus(RP) extends along the renal artery until it arrives at the substance ofthe kidney. Fibers contributing to the renal plexus (RP) arise from theceliac ganglion, the superior mesenteric ganglion, the aorticorenalganglion and the aortic plexus. The renal plexus (RP), also referred toas the renal nerve, is predominantly comprised of sympatheticcomponents. There is no (or at least very minimal) parasympatheticinnervation of the kidney.

Preganglionic neuronal cell bodies are located in the intermediolateralcell column of the spinal cord. Preganglionic axons pass through theparavertebral ganglia (they do not synapse) to become the lessersplanchnic nerve, the least splanchnic nerve, first lumbar splanchnicnerve, second lumbar splanchnic nerve, and travel to the celiacganglion, the superior mesenteric ganglion, and the aorticorenalganglion. Postganglionic neuronal cell bodies exit the celiac ganglion,the superior mesenteric ganglion, and the aorticorenal ganglion to therenal plexus (RP) and are distributed to the renal vasculature.

b. Renal Sympathetic Neural Activity

Messages travel through the SNS in a bidirectional flow. Efferentmessages may trigger changes in different parts of the bodysimultaneously. For example, the sympathetic nervous system mayaccelerate heart rate; widen bronchial passages; decrease motility(movement) of the large intestine; constrict blood vessels; increaseperistalsis in the esophagus; cause pupil dilation, piloerection (goosebumps) and perspiration (sweating); and raise blood pressure. Afferentmessages carry signals from various organs and sensory receptors in thebody to other organs and, particularly, the brain.

Hypertension, heart failure and chronic kidney disease are a few of manydisease states that result from chronic activation of the SNS,especially the renal sympathetic nervous system. Chronic activation ofthe SNS is a maladaptive response that drives the progression of thesedisease states. Pharmaceutical management of therenin-angiotensin-aldosterone system (RAAS) has been a longstanding, butsomewhat ineffective, approach for reducing over-activity of the SNS.

As mentioned above, the renal sympathetic nervous system has beenidentified as a major contributor to the complex pathophysiology ofhypertension, states of volume overload (such as heart failure), andprogressive renal disease, both experimentally and in humans. Studiesemploying radiotracer dilution methodology to measure overflow ofnorepinephrine from the kidneys to plasma revealed increased renalnorepinephrine (NE) spillover rates in patients with essentialhypertension, particularly so in young hypertensive subjects, which inconcert with increased NE spillover from the heart, is consistent withthe hemodynamic profile typically seen in early hypertension andcharacterized by an increased heart rate, cardiac output, andrenovascular resistance. It is now known that essential hypertension iscommonly neurogenic, often accompanied by pronounced sympathetic nervoussystem overactivity.

Activation of cardiorenal sympathetic nerve activity is even morepronounced in heart failure, as demonstrated by an exaggerated increaseof NE overflow from the heart and the kidneys to plasma in this patientgroup. In line with this notion is the recent demonstration of a strongnegative predictive value of renal sympathetic activation on all-causemortality and heart transplantation in patients with congestive heartfailure, which is independent of overall sympathetic activity,glomerular filtration rate, and left ventricular ejection fraction.These findings support the notion that treatment regimens that aredesigned to reduce renal sympathetic stimulation have the potential toimprove survival in patients with heart failure.

Both chronic and end stage renal disease are characterized by heightenedsympathetic nervous activation. In patients with end stage renaldisease, plasma levels of norepinephrine above the median have beendemonstrated to be predictive for both all-cause death and death fromcardiovascular disease. This is also true for patients suffering fromdiabetic or contrast nephropathy. There is compelling evidencesuggesting that sensory afferent signals originating from the diseasedkidneys are major contributors to initiating and sustaining elevatedcentral sympathetic outflow in this patient group; this facilitates theoccurrence of the well-known adverse consequences of chronic sympatheticover activity, such as hypertension, left ventricular hypertrophy,ventricular arrhythmias, sudden cardiac death, insulin resistance,diabetes, and metabolic syndrome.

i. Renal Sympathetic Efferent Activity

Sympathetic nerves to the kidneys terminate in the blood vessels, thejuxtaglomerular apparatus and the renal tubules. Stimulation of therenal sympathetic nerves causes increased renin release, increasedsodium (Na⁺) reabsorption, and a reduction of renal blood flow. Thesecomponents of the neural regulation of renal function are considerablystimulated in disease states characterized by heightened sympathetictone and clearly contribute to the rise in blood pressure inhypertensive patients. The reduction of renal blood flow and glomerularfiltration rate as a result of renal sympathetic efferent stimulation islikely a cornerstone of the loss of renal function in cardio-renalsyndrome, which is renal dysfunction as a progressive complication ofchronic heart failure, with a clinical course that typically fluctuateswith the patient's clinical status and treatment. Pharmacologicstrategies to thwart the consequences of renal efferent sympatheticstimulation include centrally acting sympatholytic drugs, beta blockers(intended to reduce renin release), angiotensin converting enzymeinhibitors and receptor blockers (intended to block the action ofangiotensin II and aldosterone activation consequent to renin release)and diuretics (intended to counter the renal sympathetic mediated sodiumand water retention). However, the current pharmacologic strategies havesignificant limitations including limited efficacy, compliance issues,side effects and others.

ii. Renal Sensory Afferent Nerve Activity

The kidneys communicate with integral structures in the central nervoussystem via renal sensory afferent nerves. Several forms of “renalinjury” may induce activation of sensory afferent signals. For example,renal ischemia, reduction in stroke volume or renal blood flow, or anabundance of adenosine enzyme may trigger activation of afferent neuralcommunication. As shown in FIGS. 10 and 11, this afferent communicationmight be from the kidney to the brain or might be from one kidney to theother kidney (via the central nervous system). These afferent signalsare centrally integrated and may result in increased sympatheticoutflow. This sympathetic drive is directed towards the kidneys, therebyactivating the RAAS and inducing increased renin secretion, sodiumretention, volume retention and vasoconstriction. Central sympatheticover activity also impacts other organs and bodily structures innervatedby sympathetic nerves such as the heart and the peripheral vasculature,resulting in the described adverse effects of sympathetic activation,several aspects of which also contribute to the rise in blood pressure.

The physiology therefore suggests that (i) modulation of tissue withefferent sympathetic nerves will reduce inappropriate renin release,salt retention, and reduction of renal blood flow, and that (ii)modulation of tissue with afferent sensory nerves will reduce thesystemic contribution to hypertension and other disease statesassociated with increased central sympathetic tone through its directeffect on the posterior hypothalamus as well as the contralateralkidney. In addition to the central hypotensive effects of afferent renaldenervation, a desirable reduction of central sympathetic outflow tovarious other sympathetically innervated organs such as the heart andthe vasculature is anticipated.

2. Additional Clinical Benefits of Renal Denervation

As provided above, renal denervation is likely to be valuable in thetreatment of several clinical conditions characterized by increasedoverall and particularly renal sympathetic activity such ashypertension, metabolic syndrome, insulin resistance, diabetes, leftventricular hypertrophy, chronic end stage renal disease, inappropriatefluid retention in heart failure, cardio-renal syndrome, and suddendeath. Since the reduction of afferent neural signals contributes to thesystemic reduction of sympathetic tone/drive, renal denervation mightalso be useful in treating other conditions associated with systemicsympathetic hyperactivity. Accordingly, renal denervation may alsobenefit other organs and bodily structures innervated by sympatheticnerves, including those identified in FIG. 8. For example, as previouslydiscussed, a reduction in central sympathetic drive may reduce theinsulin resistance that afflicts people with metabolic syndrome and TypeII diabetics. Additionally, patients with osteoporosis are alsosympathetically activated and might also benefit from the downregulation of sympathetic drive that accompanies renal denervation.

3. Achieving Intravascular Access to the Renal Artery

In accordance with the present technology, neuromodulation of a leftand/or right renal plexus (RP), which is intimately associated with aleft and/or right renal artery, may be achieved through intravascularaccess. As FIG. 12 shows, blood moved by contractions of the heart isconveyed from the left ventricle of the heart by the aorta. The aortadescends through the thorax and branches into the left and right renalarteries. Below the renal arteries, the aorta bifurcates at the left andright iliac arteries. The left and right iliac arteries descend,respectively, through the left and right legs and join the left andright femoral arteries.

As FIG. 13 shows, the blood collects in veins and returns to the heart,through the femoral veins into the iliac veins and into the inferiorvena cava. The inferior vena cava branches into the left and right renalveins. Above the renal veins, the inferior vena cava ascends to conveyblood into the right atrium of the heart. From the right atrium, theblood is pumped through the right ventricle into the lungs, where it isoxygenated. From the lungs, the oxygenated blood is conveyed into theleft atrium. From the left atrium, the oxygenated blood is conveyed bythe left ventricle back to the aorta.

As will be described in greater detail later, the femoral artery may beaccessed and cannulated at the base of the femoral triangle justinferior to the midpoint of the inguinal ligament. A catheter may beinserted percutaneously into the femoral artery through this accesssite, passed through the iliac artery and aorta, and placed into eitherthe left or right renal artery. This comprises an intravascular paththat offers minimally invasive access to a respective renal arteryand/or other renal blood vessels.

The wrist, upper arm, and shoulder region provide other locations forintroduction of catheters into the arterial system. For example,catheterization of either the radial, brachial, or axillary artery maybe utilized in select cases. Catheters introduced via these accesspoints may be passed through the subclavian artery on the left side (orvia the subclavian and brachiocephalic arteries on the right side),through the aortic arch, down the descending aorta and into the renalarteries using standard angiographic technique.

4. Properties and Characteristics of the Renal Vasculature

Since neuromodulation of a left and/or right renal plexus (RP) may beachieved in accordance with the present technology through intravascularaccess, properties and characteristics of the renal vasculature mayimpose constraints upon and/or inform the design of apparatus, systems,and methods for achieving such renal neuromodulation. Some of theseproperties and characteristics may vary across the patient populationand/or within a specific patient across time, as well as in response todisease states, such as hypertension, chronic kidney disease, vasculardisease, end-stage renal disease, insulin resistance, diabetes,metabolic syndrome, etc. These properties and characteristics, asexplained herein, may have bearing on the efficacy of the procedure andthe specific design of the intravascular device. Properties of interestmay include, for example, material/mechanical, spatial, fluiddynamic/hemodynamic and/or thermodynamic properties.

As discussed previously, a catheter may be advanced percutaneously intoeither the left or right renal artery via a minimally invasiveintravascular path. However, minimally invasive renal arterial accessmay be challenging, for example, because as compared to some otherarteries that are routinely accessed using catheters, the renal arteriesare often extremely tortuous, may be of relatively small diameter,and/or may be of relatively short length. Furthermore, renal arterialatherosclerosis is common in many patients, particularly those withcardiovascular disease. Renal arterial anatomy also may varysignificantly from patient to patient, which further complicatesminimally invasive access. Significant inter-patient variation may beseen, for example, in relative tortuosity, diameter, length, and/oratherosclerotic plaque burden, as well as in the take-off angle at whicha renal artery branches from the aorta. Apparatus, systems and methodsfor achieving renal neuromodulation via intravascular access shouldaccount for these and other aspects of renal arterial anatomy and itsvariation across the patient population when minimally invasivelyaccessing a renal artery.

In addition to complicating renal arterial access, specifics of therenal anatomy also complicate establishment of stable contact betweenneuromodulatory apparatus and a luminal surface or wall of a renalartery. For example, navigation can be impeded by the tight space withina renal artery, as well as tortuosity of the artery. Furthermore,establishing consistent contact is complicated by patient movement,respiration, and/or the cardiac cycle because these factors may causesignificant movement of the renal artery relative to the aorta, and thecardiac cycle may transiently distend the renal artery (i.e. cause thewall of the artery to pulse).

Even after accessing a renal artery and facilitating stable contactbetween neuromodulatory apparatus and a luminal surface of the artery,nerves in and around the adventia of the artery should be safelymodulated via the neuromodulatory apparatus. Effectively applyingthermal treatment from within a renal artery is non-trivial given thepotential clinical complications associated with such treatment. Forexample, the intima and media of the renal artery are highly vulnerableto thermal injury. As discussed in greater detail below, theintima-media thickness separating the vessel lumen from its adventitiameans that target renal nerves may be multiple millimeters distant fromthe luminal surface of the artery. Sufficient energy should be deliveredto or heat removed from the target renal nerves to modulate the targetrenal nerves without excessively cooling or heating the vessel wall tothe extent that the wall is frozen, desiccated, or otherwise potentiallyaffected to an undesirable extent. A potential clinical complicationassociated with excessive heating is thrombus formation from coagulatingblood flowing through the artery. Given that this thrombus may cause akidney infarct, thereby causing irreversible damage to the kidney,thermal treatment from within the renal artery should be appliedcarefully. Accordingly, the complex fluid mechanics and thermodynamicconditions present in the renal artery during treatment, particularlythose that may impact heat transfer dynamics at the treatment site, maybe important in applying energy (e.g., heating thermal energy) and/orremoving heat from the tissue (e.g., cooling thermal conditions) fromwithin the renal artery.

The neuromodulatory apparatus should also be configured to allow foradjustable positioning and repositioning of the energy delivery elementwithin the renal artery since location of treatment may also impactclinical efficacy. For example, it may be tempting to apply a fullcircumferential treatment from within the renal artery given that therenal nerves may be spaced circumferentially around a renal artery. Insome situations, a full-circle lesion likely resulting from a continuouscircumferential treatment may be potentially related to renal arterystenosis. Therefore, the formation of more complex lesions along alongitudinal dimension of the renal artery and/or repositioning of theneuromodulatory apparatus to multiple treatment locations may bedesirable. It should be noted, however, that a benefit of creating acircumferential ablation may outweigh the potential of renal arterystenosis or the risk may be mitigated with certain embodiments or incertain patients and creating a circumferential ablation could be agoal. Additionally, variable positioning and repositioning of theneuromodulatory apparatus may prove to be useful in circumstances wherethe renal artery is particularly tortuous or where there are proximalbranch vessels off the renal artery main vessel, making treatment incertain locations challenging. Manipulation of a device in a renalartery should also consider mechanical injury imposed by the device onthe renal artery. Motion of a device in an artery, for example byinserting, manipulating, negotiating bends and so forth, may contributeto dissection, perforation, denuding intima, or disrupting the interiorelastic lamina.

Blood flow through a renal artery may be temporarily occluded for ashort time with minimal or no complications. However, occlusion for asignificant amount of time should be avoided because to prevent injuryto the kidney such as ischemia. It could be beneficial to avoidocclusion all together or, if occlusion is beneficial to the embodiment,to limit the duration of occlusion, for example to 2-5 minutes.

Based on the above described challenges of (1) renal arteryintervention, (2) consistent and stable placement of the treatmentelement against the vessel wall, (3) effective application of treatmentacross the vessel wall, (4) positioning and potentially repositioningthe treatment apparatus to allow for multiple treatment locations, and(5) avoiding or limiting duration of blood flow occlusion, variousindependent and dependent properties of the renal vasculature that maybe of interest include, for example, (a) vessel diameter, vessel length,intima-media thickness, coefficient of friction, and tortuosity; (b)distensibility, stiffness and modulus of elasticity of the vessel wall;(c) peak systolic, end-diastolic blood flow velocity, as well as themean systolic-diastolic peak blood flow velocity, and mean/maxvolumetric blood flow rate; (d) specific heat capacity of blood and/orof the vessel wall, thermal conductivity of blood and/or of the vesselwall, and/or thermal convectivity of blood flow past a vessel walltreatment site and/or radiative heat transfer; (e) renal artery motionrelative to the aorta induced by respiration, patient movement, and/orblood flow pulsatility; and (f) the take-off angle of a renal arteryrelative to the aorta. These properties will be discussed in greaterdetail with respect to the renal arteries. However, dependent on theapparatus, systems and methods utilized to achieve renalneuromodulation, such properties of the renal arteries, also may guideand/or constrain design characteristics.

As noted above, an apparatus positioned within a renal artery shouldconform to the geometry of the artery. Renal artery vessel diameter,D_(RA), typically is in a range of about 2-10 mm, with most of thepatient population having a D_(RA) of about 4 mm to about 8 mm and anaverage of about 6 mm. Renal artery vessel length, L_(RA), between itsostium at the aorta/renal artery juncture and its distal branchings,generally is in a range of about 5-70 mm, and a significant portion ofthe patient population is in a range of about 20-50 mm. Since the targetrenal plexus is embedded within the adventitia of the renal artery, thecomposite Intima-Media Thickness, IMT, (i.e., the radial outwarddistance from the artery's luminal surface to the adventitia containingtarget neural structures) also is notable and generally is in a range ofabout 0.5-2.5 mm, with an average of about 1.5 mm. Although a certaindepth of treatment is important to reach the target neural fibers, thetreatment should not be too deep (e.g., >5 mm from inner wall of therenal artery) to avoid non-target tissue and anatomical structures suchas the renal vein.

An additional property of the renal artery that may be of interest isthe degree of renal motion relative to the aorta induced by respirationand/or blood flow pulsatility. A patient's kidney, which is located atthe distal end of the renal artery, may move as much as 4″ craniallywith respiratory excursion. This may impart significant motion to therenal artery connecting the aorta and the kidney, thereby requiring fromthe neuromodulatory apparatus a unique balance of stiffness andflexibility to maintain contact between the energy delivery element andthe vessel wall during cycles of respiration. Furthermore, the take-offangle between the renal artery and the aorta may vary significantlybetween patients, and also may vary dynamically within a patient, e.g.,due to kidney motion. The take-off angle generally may be in a range ofabout 30°-135°.

F. Additional Examples

Several aspects of the present technology are set forth in the followingexamples.

1. A neuromodulation system, comprising:

-   -   a catheter including—        -   an elongated shaft having a distal portion configured to be            intravascularly positioned at a treatment site within a            renal blood vessel of a human patient;        -   a plurality of electrodes spaced apart along the distal            portion of the shaft, wherein the electrodes are configured            to deliver neuromodulation energy to target nerves at or            adjacent the treatment site; and        -   an irrigation outlet proximal to the electrode; and    -   a controller configured to be communicatively coupled to the        neuromodulation element, wherein the controller is further        configured to monitor a parameter of at least one of the        electrodes and tissue at or adjacent the treatment site,    -   wherein the irrigation outlet is configured to direct irrigation        fluid in a first direction based, at least in part, on        instructions from the controller corresponding to the monitored        parameter.

2. The neuromodulation system of example 1 wherein the first directionis parallel with a longitudinal axis of the renal blood vessel.

3. The neuromodulation system of examples 1 or 2, further comprising—

-   -   an energy generator external to the patient and electrically        coupled to the plurality of electrodes and the controller; and    -   an irrigation pump operably coupled to the irrigation outlet and        the controller,    -   wherein the controller is further configured to cause the energy        generator to deliver neuromodulation energy via the electrodes        and cause the irrigation pump to deliver irrigation fluid via        the irrigation outlet.

4. The neuromodulation system of example 3 wherein the controller isfurther configured to—

-   -   compare the parameter to a predetermined parameter profile        range;    -   cause the energy generator to deliver neuromodulation energy at        a power level in accordance with a control algorithm when the        parameter is within the range;    -   cause the energy generator to deliver irrigation fluid at a        temperature and flow rate in accordance with the control        algorithm when the parameter is within the range; and    -   modify the control algorithm to adjust a characteristic of at        least one of the energy and the irrigation fluid when the        parameter is outside of the range.

5. The neuromodulation system of example 4 wherein the parameter is atemperature of one of the electrodes, and wherein the characteristic isa power level at which the energy is delivered, and further wherein thecontroller is configured to decrease the power level when thetemperature of the electrodes is outside of the range.

6. The neuromodulation system of example 4 wherein the parameter is atemperature of one of the electrodes, and wherein the characteristic isa power level at which the energy is delivered, and further wherein thecontroller is configured to hold the power level constant or decreasethe power level when the temperature of the electrode is outside of therange.

7. The neuromodulation system of examples 4 or 6 wherein the parameteris a temperature of the one of the electrodes, and wherein thecharacteristic is a flow rate or a temperature at which the irrigationfluid is delivered, and further wherein the controller is configured toincrease the flow rate or decrease the temperature at which theirrigation fluid is delivered when the temperature of the electrode isoutside of the range.

8. A system, comprising:

-   -   a neuromodulation catheter including—        -   an elongated shaft having a distal portion sized and shaped            to be intravascularly positioned at a treatment site within            a blood vessel of a human patient;        -   an electrode configured to deliver radio frequency (RF)            energy to target nerves at or adjacent the treatment site,            wherein the electrode is configured to deliver the RF energy            in accordance with a control algorithm; and        -   a plurality of irrigation outlets positioned to release            irrigation fluid in accordance with the control algorithm;    -   an irrigation pump coupled to the plurality of irrigation        outlets, the irrigation pump configured to deliver the        irrigation fluid to the treatment site via the plurality of        irrigation outlets;    -   an energy generator external to the patient and coupled to the        electrode and to the irrigation pump, wherein the energy        generator is configured to deliver the RF energy to the target        nerves via the electrode; and    -   a controller communicatively coupled to the electrode, the        energy generator, and the irrigation pump, wherein the        controller is further configured to monitor a parameter of at        least one of the electrode and tissue at or adjacent the        treatment site.

9. The system of example 8 wherein a first subset of the plurality ofirrigation outlets are located proximal to the electrode, and whereinthe first subset of irrigation outlets are each oriented to directirrigation fluid in a first direction.

10. The system of example 9 wherein the electrode is a first electrode,and wherein the system further comprises a second electrode on theelongated shaft spaced apart from the first electrode, and wherein thesecond electrode is located between the first electrode and a distal endof the elongated shaft, and further wherein the first subset isconfigured to release the irrigation fluid such that the irrigationfluid cools the second electrode.

11. The system of example 8 wherein the plurality of irrigation outletsare located on the elongated shaft between the electrode and a proximalportion of the elongated shaft.

12. The system of examples 10 or 11 wherein the plurality of irrigationoutlets are each oriented to direct irrigation fluid radially outwardfrom the elongated shaft.

13. The system of example 8 wherein the neuromodulation catheter furthercomprises an irrigation ring, and wherein the plurality of irrigationoutlets are positioned on the irrigation ring.

14. The system of examples 8, 9, 10, 11, 12, or 13 wherein the parameteris a temperature of the electrode, and wherein the controller is furtherconfigured to increase a power level at which the energy generatordelivers the neuromodulation energy while maintaining the temperature ofthe electrode within a predetermined temperature profile range.

15. The system of example 14, wherein while the controller increases thepower level, the controller is further configured to (i) maintain orincrease a flow rate and/or (ii) maintain or decrease a temperature atwhich the irrigation pump delivers the irrigation fluid.

16. The system of example 15 wherein the controller is configured toincrease the power level only with an increase in the flow rate and/oronly with a decrease in the temperature of the irrigation fluid.

17. The system of examples 8, 9, 10, 11, 12, 13, 14, 15, or 16 whereinthe controller is configured to prevent the energy generator fromincreasing a power level at which the energy generator delivers theneuromodulation energy when the irrigation fluid delivered by theirrigation pump reaches a maximum flow rate and/or a minimumtemperature.

18. A method, comprising:

-   -   positioning a neuromodulation catheter at a treatment site        within a renal blood vessel of a human patient, wherein the        neuromodulation catheter includes a treatment assembly having        one or more electrodes and one or more irrigation outlets;    -   deploying the treatment assembly such that the one or more        electrodes contact the blood vessel at the treatment site;    -   delivering neuromodulation energy in accordance with a control        algorithm via the one or more electrodes;    -   monitoring a temperature of the one or more electrodes and/or a        temperature of tissue of the blood vessel at or proximate to the        treatment site; and    -   delivering irrigation fluid corresponding, at least in part, to        the neuromodulation energy and the monitored temperature via the        one or more irrigation outlets.

19. The method of example 18 wherein delivering the neuromodulationenergy in accordance with the control algorithm includes increasing apower level of the neuromodulation energy, and wherein delivering theirrigation fluid includes delivering the irrigation fluid at anincreased flow rate and/or a decreased temperature corresponding to theincreased power level.

20. The method of example 19, further comprising maintaining thetemperature of the one or more electrodes constant and/or within anacceptable temperature range while the power level is increased.

21. The method of examples 18, 19, or 20, further comprising comparingthe temperature of the one or more electrodes and/or the temperature ofthe tissue to a predetermined temperature profile range, and whereindelivering the neuromodulation energy in accordance with the controlalgorithm includes—

-   -   maintaining or decreasing a power level of the neuromodulation        energy when the temperature of the one or more electrodes and/or        the temperature of the tissue is outside of the range; and/or    -   increasing the power level at a slower rate when the temperature        of the one or more electrodes and/or the temperature of the        tissue is outside of the range.

22. The method of examples 18, 19, 20, or 21, further comprisingcomparing the temperature of the one or more electrodes and/or thetemperature of the tissue to a predetermined temperature profile range,and wherein delivering the irrigation fluid includes delivering theirrigation fluid at an increased flow rate and/or a decreasedtemperature when the temperature of the one or more electrodes and/orthe temperature of the tissue is outside of the range.

23. The method of examples 18, 19, 20, 21, or 22, further comprising:

-   -   comparing the temperature of the one or more electrodes and/or        the temperature of the tissue to a predetermined temperature        profile range;    -   when the temperature of the one or more electrodes and/or the        temperature of the tissue is outside of the range, delivering        irrigation fluid to the treatment site via the one or more        irrigation outlets; and    -   when the temperature of the one or more electrodes and/or the        temperature of the tissue is inside of the range, increasing a        power level at which the neuromodulation energy is delivered.

G. Conclusion

The above detailed descriptions of embodiments of the technology are notintended to be exhaustive or to limit the technology to the precise formdisclosed above. Although specific embodiments of, and examples for, thetechnology are described above for illustrative purposes, variousequivalent modifications are possible within the scope of thetechnology, as those skilled in the relevant art will recognize. Forexample, while steps are presented in a given order, alternativeembodiments may perform steps in a different order. Furthermore, thevarious embodiments described herein may also be combined to providefurther embodiments.

From the foregoing, it will be appreciated that specific embodiments ofthe technology have been described herein for purposes of illustration,but well-known structures and functions have not been shown or describedin detail to avoid unnecessarily obscuring the description of theembodiments of the technology. Where the context permits, singular orplural terms may also include the plural or singular term, respectively.Moreover, unless the word “or” is expressly limited to mean only asingle item exclusive from the other items in reference to a list of twoor more items, then the use of “or” in such a list is to be interpretedas including (a) any single item in the list, (b) all of the items inthe list, or (c) any combination of the items in the list. Where thecontext permits, singular or plural terms may also include the plural orsingular term, respectively. Additionally, the terms “comprising,”“including,” “having” and “with” are used throughout to mean includingat least the recited feature(s) such that any greater number of the samefeature and/or additional types of other features are not precluded.

From the foregoing, it will also be appreciated that variousmodifications may be made without deviating from the technology. Forexample, various components of the technology can be further dividedinto subcomponents, or that various components and functions of thetechnology may be combined and/or integrated. Furthermore, althoughadvantages associated with certain embodiments of the technology havebeen described in the context of those embodiments, other embodimentsmay also exhibit such advantages, and not all embodiments neednecessarily exhibit such advantages to fall within the scope of thetechnology. Accordingly, the disclosure and associated technology canencompass other embodiments not expressly shown or described herein.

I claim:
 1. A neuromodulation system comprising: a catheter including:an elongated shaft having a distal portion configured to beintravascularly positioned at a treatment site within a renal bloodvessel of a human patient; a plurality of electrodes spaced apart alongthe distal portion of the elongated shaft, wherein the plurality ofelectrodes are configured to deliver neuromodulation energy to targetnerves at or adjacent the treatment site; and an irrigation outletproximal to an electrode of the plurality of electrodes and configuredto output irrigation fluid; and a controller configured to becommunicatively coupled to the plurality of electrodes, wherein thecontroller is configured to: monitor a temperature of at least oneelectrode of the plurality of electrodes or tissue at or adjacent thetreatment site or a power level of at least one electrode of theplurality of electrodes; cause one or more of an increase in a flow rateof delivery of the irrigation fluid or a decrease in a temperature ofthe irrigation fluid to be output from the irrigation outlet when themonitored temperature of the at least one electrode of the plurality ofelectrodes or tissue at or adjacent the treatment site or the monitoredpower level of the at least one electrode of the plurality of electrodesincreases; and to prevent the neuromodulation system from determining aninaccurate measurement of ablation progress, prevent the flow rate ofthe irrigation fluid from increasing above a flow rate threshold, andprevent the temperature of the irrigation fluid from decreasing below atemperature threshold.
 2. The neuromodulation system of claim 1 whereinthe irrigation outlet is further configured to direct the irrigationfluid in a first direction that is parallel with a longitudinal axis ofthe renal blood vessel.
 3. The neuromodulation system of claim 1,further comprising: an energy generator external to the human patientand electrically coupled to the plurality of electrodes and thecontroller; and an irrigation pump operably coupled to the irrigationoutlet and the controller, wherein the controller is further configuredto cause the energy generator to deliver the neuromodulation energy viathe plurality of electrodes and cause the irrigation pump to deliver theirrigation fluid via the irrigation outlet.
 4. The neuromodulationsystem of claim 3 wherein the controller is further configured to:compare the monitored temperature or the monitored power level to apredetermined parameter profile range; cause the energy generator todeliver the neuromodulation energy at a power level in accordance with acontrol algorithm when the monitored temperature or the monitored powerlevel is within the predetermined parameter profile range; cause theenergy generator to deliver the irrigation fluid at a temperature andflow rate in accordance with the control algorithm when the monitoredtemperature or the monitored power level is within the predeterminedparameter profile range; and modify the control algorithm to adjust acharacteristic of at least one of the neuromodulation energy or theirrigation fluid when the monitored temperature or the monitored powerlevel is outside of the predetermined parameter profile range.
 5. Theneuromodulation system of claim 4 wherein the monitored temperature is atemperature of one electrode of the plurality of electrodes, and whereinthe characteristic is the power level at which the neuromodulationenergy is delivered, and further wherein the controller is configured todecrease the power level at which the neuromodulation energy isdelivered when the temperature of the one electrode of the plurality ofelectrodes is outside of the predetermined parameter profile range. 6.The neuromodulation system of claim 4 wherein the monitored temperatureis a temperature of one electrode of the plurality of electrodes, andwherein the characteristic is the power level at which theneuromodulation energy is delivered, and further wherein the controlleris configured to hold the power level at which the neuromodulationenergy is delivered constant or decrease the power level at which theneuromodulation energy is delivered when the temperature of the oneelectrode of the plurality of electrodes is outside of the predeterminedparameter profile range.
 7. The neuromodulation system of claim 4wherein the monitored temperature is a temperature of the one electrodeof the plurality of electrodes, and wherein the characteristic is thetemperature of the irrigation fluid to be output from the irrigationoutlet or the flow rate at which the irrigation fluid is delivered, andfurther wherein the controller is configured to increase the flow rateor decrease the temperature at which the irrigation fluid is deliveredwhen the temperature of the one electrode of the plurality of electrodesis outside of the predetermined parameter profile range.
 8. Theneuromodulation system of claim 4 wherein the monitored temperature isthe temperature of the one electrode of the plurality of electrodes, andwherein the characteristic is the temperature of the irrigation fluid tobe output from the irrigation outlet or the flow rate at which theirrigation fluid is delivered, and further wherein the controller isconfigured to increase the flow rate or decrease the temperature atwhich the irrigation fluid is delivered when the temperature of the oneelectrode of the plurality of electrodes is outside of the predeterminedparameter profile range.
 9. A system comprising: a neuromodulationcatheter including: an elongated shaft having a distal portion sized andshaped to be intravascularly positioned at a treatment site within ablood vessel of a human patient; an electrode configured to deliverradio frequency (RF) energy to target nerves at or adjacent thetreatment site, wherein the electrode is configured to deliver the RFenergy in accordance with a control algorithm; and a plurality ofirrigation outlets positioned to release irrigation fluid in accordancewith the control algorithm; an irrigation pump coupled to the pluralityof irrigation outlets, the irrigation pump configured to deliver theirrigation fluid to the treatment site via the plurality of irrigationoutlets; an energy generator external to the human patient and coupledto the electrode and to the irrigation pump, wherein the energygenerator is configured to deliver the RF energy to the target nervesvia the electrode; and a controller communicatively coupled to theelectrode, the energy generator, and the irrigation pump, wherein thecontroller is further configured to: monitor a temperature of at leastone of the electrode or tissue at or adjacent the treatment site or apower level of the electrode; cause one or more of an increase in a flowrate of delivery of the irrigation fluid that is delivered or a decreasein a temperature of the irrigation fluid to be output from theirrigation outlets when the temperature of the at least one of theelectrode or tissue at or adjacent the treatment site or the power levelof the electrode increases; and to prevent the system from determiningan inaccurate measurement of ablation progress, prevent the flow rate ofthe irrigation fluid from increasing above a flow rate threshold, andprevent the temperature of the irrigation fluid from decreasing below atemperature threshold.
 10. The system of claim 9 wherein a first subsetof the plurality of irrigation outlets are located proximal to theelectrode, and wherein the first subset of irrigation outlets are eachoriented to direct irrigation fluid in a first direction.
 11. The systemof claim 10 wherein the electrode is a first electrode, and wherein thesystem further comprises a second electrode on the elongated shaftspaced apart from the first electrode, wherein the second electrode islocated between the first electrode and a distal end of the elongatedshaft, and further wherein the first subset is configured to release theirrigation fluid such that the irrigation fluid cools the secondelectrode.
 12. The system of claim 9 wherein the plurality of irrigationoutlets are located on the elongated shaft between the electrode and aproximal portion of the elongated shaft.
 13. The system of claim 9wherein the plurality of irrigation outlets are each oriented to directirrigation fluid radially outward from the elongated shaft.
 14. Thesystem of claim 9 wherein the neuromodulation catheter further comprisesan irrigation ring, and wherein the plurality of irrigation outlets arepositioned on the irrigation ring.
 15. The system of claim 9 wherein themonitored temperature is a temperature of the electrode, and wherein thecontroller is further configured to increase a power level at which theenergy generator delivers the RF energy while maintaining thetemperature of the electrode within a predetermined temperature profilerange.
 16. The system of claim 15, wherein while the controllerincreases the power level at which the energy generator delivers the RFenergy, the controller is further configured to (i) maintain or increasea flow rate or (ii) maintain or decrease a temperature at which theirrigation pump delivers the irrigation fluid.
 17. The system of claim 9wherein the controller is configured to only increase the flow rate oronly decrease the temperature of the irrigation fluid to be output fromthe irrigation outlets when the power level of the electrode increases.18. The system of claim 9 wherein the controller is configured toprevent the energy generator from increasing a power level at which theenergy generator delivers the RF energy when the irrigation fluiddelivered by the irrigation pump reaches a maximum flow rate or aminimum temperature.
 19. A method comprising: positioning aneuromodulation catheter at a treatment site within a renal blood vesselof a human patient, wherein the neuromodulation catheter includes atreatment assembly having one or more electrodes and one or moreirrigation outlets; deploying the treatment assembly such that the oneor more electrodes contact the blood vessel at the treatment site;delivering neuromodulation energy in accordance with a control algorithmvia the one or more electrodes; monitoring a temperature of the one ormore electrodes and/or a temperature of tissue of the blood vessel at orproximate to the treatment site or a power level of at least oneelectrode of the one or more electrodes; delivering irrigation fluidcorresponding, at least in part, to the neuromodulation energy and themonitored temperature via the one or more irrigation outlets; and toprevent determining an inaccurate measurement of ablation progress,preventing the flow rate of the irrigation fluid from increasing above aflow rate threshold, and preventing the temperature of the irrigationfluid to be output from the irrigation outlet from decreasing below atemperature threshold.
 20. The method of claim 19 wherein delivering theneuromodulation energy in accordance with the control algorithm includesincreasing a power level of the neuromodulation energy, and whereindelivering the irrigation fluid includes delivering the irrigation fluidat an increased flow rate and/or a decreased temperature correspondingto the increased power level.
 21. The method of claim 20, furthercomprising maintaining the temperature of the one or more electrodesconstant and/or within an acceptable temperature range while the powerlevel is increased.
 22. The method of claim 19, further comprisingcomparing the temperature of the one or more electrodes and/or thetemperature of the tissue to a predetermined temperature profile range,and wherein delivering the neuromodulation energy in accordance with thecontrol algorithm includes- maintaining or decreasing a power level ofthe neuromodulation energy when the temperature of the one or moreelectrodes and/or the temperature of the tissue is outside of the range;and/or increasing the power level at a slower rate when the temperatureof the one or more electrodes and/or the temperature of the tissue isoutside of the range.
 23. The method of claim 19, further comprisingcomparing the temperature of the one or more electrodes and/or thetemperature of the tissue to a predetermined temperature profile range,and wherein delivering the irrigation fluid includes delivering theirrigation fluid at an increased flow rate and/or a decreasedtemperature when the temperature of the one or more electrodes and/orthe temperature of the tissue is outside of the range.
 24. The method ofclaim 19, further comprising: comparing the temperature of the one ormore electrodes and/or the temperature of the tissue to a predeterminedtemperature profile range; when the temperature of the one or moreelectrodes and/or the temperature of the tissue is outside of the range,delivering irrigation fluid to the treatment site via the one or moreirrigation outlets; and when the temperature of the one or moreelectrodes and/or the temperature of the tissue is inside of the range,increasing a power level at which the neuromodulation energy isdelivered.